Podcasts about Bacteroides

Matters Microbial #87: Dietary Protein and the Microbiome April 17, 2025 Today, Dr. Manuel Kleiner, Associate Professor of Microbiomes and Complex Microbial Communities at North Carolina State University,  joins the #QualityQuorum to discuss how diet can influence the microbiome in fascinating ways. Host: Mark O. Martin Guest: Manuel Kleiner Subscribe: Apple Podcasts, Spotify Become a patron of Matters Microbial! Links for this episode An overview of “pink pigmented facultative methylotrophs,” which can lead to wonderful “leaf prints.” Gnotobiotic versus “germ-free” animals. A solid review of the gut microbiome and the relationship to health. An article describing how proteins are digested by the microbiota. A description of glycan degrading enzymes and the gut microbiome. An overview of mucin. Description of metaproteomics by Dr. Kleiner. Description of metagenomics. Gut microbiota and dysbiosis. An overview of inflammatory bowel disease. An overview of Bacteroides thetaiotaomicron. An overview of Akkermansia muciniphila. The possibility of microbes “farming” us for mucus! The wide ranging and deeply fascinating website for Dr. Kleiner's research group. Dr. Kleiner's faculty website. Intro music is by Reber Clark Send your questions and comments to mattersmicrobial@gmail.com

Story at-a-glance Introducing a wide variety of plant-based foods after age one speeds up gut microbiome maturity, helping your child build better digestion and stronger immunity early on Children who consume diverse plant fibers develop higher levels of beneficial bacteria like Faecalibacterium and Bacteroides, which reduce inflammation and protect the gut lining Between 12 and 18 months is the most important window to introduce a range of solid foods, laying the groundwork for a healthy, adult-like gut by age 2 Local, fiber-rich foods like millet, banana, and rice work best in supporting gut health — expensive superfoods are not necessary for strong gut development Restrictive or processed replacement foods damage gut bacteria balance, but breastfeeding combined with diverse, real foods builds a more resilient, long-term gut foundation

On episode #73 of the Infectious Disease Puscast, Daniel and Sara review the infectious disease literature for the weeks of 1/16/25 – 1/29/25. Hosts: Daniel Griffin and Sara Dong Subscribe (free): Apple Podcasts, RSS, email Become a patron of Puscast! Links for this episode Viral AGA clinical practice guideline on the prevention and treatment of hepatitis B virus reactivation (Gastroenterology) Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients (Nature Communications) Insect-specific RNA viruses detection in Field-Caught Aedes aegypti mosquitoes from Argentina using NGS technology (PLoS Neglected Tropical Diseases) Bacterial Oral regimens for rifampin-resistant, fluoroquinolone-susceptible tuberculosis (NEJM) Impact of antibiotic treatment and predictors for subsequent infections in multidrug-resistant Pseudomonas aeruginosa catheter-associated asymptomatic bacteriuria (American Journal of Infection Control) Identification of the skip phenomenon among patients With Staphylococcus lugdunensis infective endocarditis (OFID) Emergence of infective endocarditis due to Serratia spp. (OFID) Reduction of vancomycin-associated acute kidney injury with montelukast (JID) Fungal The Last of US Season 2 (YouTube) Pulmonary co-infection of Pneumocystis jirovecii and Aspergillus species (OFID) Impact of fluconazoleon outcomes of patients with primary pulmonary coccidioidomycosis (CID) Parasitic Comparative outcomes of Babesiosis in immunocompromised and non-immunocompromised hosts (CID) Miscellaneous Hidradenitis suppurativa (LANCET) A severe case associated with mixed infections of Pasteurella multocida, Bacteroides pyogenes and Fusobacterium necrophorum due to a snow leopard bite (CMI: Clinical Microbiology and Infection) INSIDE-OUT: Introduction of speakers at IDWeek events (OFID) Music is by Ronald Jenkees Information on this podcast should not be considered as medical advice.

We discuss the recognition and treatment of necrotizing fasciitis. Hosts: Aurnee Rahman, MD Brian Gilberti, MD https://media.blubrry.com/coreem/content.blubrry.com/coreem/Necrotizing_Fasciitis.mp3 Download Leave a Comment Tags: Critical Care, General Surgery Show Notes Table of Contents 0:00 – Introduction 0:41 – Overview 1:10 – Types of Necrotizing Fasciitis 2:21 – Pathophysiology & Risk Factors 3:16 – Clinical Presentation 4:06 – Diagnosis 5:37 – Treatment 7:09 – Prognosis and Recovery 7:37 – Take Home points Introduction Necrotizing soft tissue infections can be easily missed in routine cases of soft tissue infection. High mortality and morbidity underscore the need for vigilance. Definition A rapidly progressive, life-threatening infection of the deep soft tissues. Involves fascia and subcutaneous fat, causing fulminant tissue destruction. High mortality often due to delayed recognition and treatment. Types of Necrotizing Fasciitis Type I (Polymicrobial) Involves aerobic and anaerobic organisms (e.g., Bacteroides, Clostridium, Peptostreptococcus). Common in immunocompromised patients or those with comorbid...

Le jeûne, notamment sous forme de restriction énergétique intermittente (REI), influence significativement le cerveau humain. Une étude publiée en décembre 2023 dans Frontiers in Cellular and Infection Microbiology a exploré ces effets en examinant les modifications de l'activité cérébrale et du microbiome intestinal chez des individus obèses soumis à un programme de REI. Méthodologie de l'étude Les chercheurs ont suivi 25 participants obèses sur une période de 62 jours. Le protocole comprenait des phases de restriction calorique alternant avec des périodes d'alimentation normale. L'activité cérébrale des participants a été évaluée à l'aide de l'imagerie par résonance magnétique fonctionnelle (IRMf), tandis que des analyses métagénomiques ont été réalisées sur des échantillons fécaux pour étudier le microbiome intestinal. Résultats principaux 1. Perte de poids et amélioration métabolique : Les participants ont perdu en moyenne 7,6 kg, soit 7,8 % de leur poids initial. Cette perte de poids s'est accompagnée d'améliorations des paramètres métaboliques, notamment une diminution de la pression artérielle et des niveaux de glucose plasmatique à jeun. 2. Modifications de l'activité cérébrale : L'IRMf a révélé des réductions de l'activité dans des régions cérébrales associées à la régulation de l'appétit et aux mécanismes d'addiction, telles que le gyrus frontal inférieur orbital gauche. Ces changements suggèrent une diminution de la réactivité aux signaux alimentaires et une meilleure maîtrise de l'impulsivité alimentaire. 3. Altérations du microbiome intestinal : L'analyse métagénomique a montré une augmentation de l'abondance de bactéries bénéfiques, notamment Faecalibacterium prausnitzii, Parabacteroides distasonis et Bacteroides uniformis, parallèlement à une diminution de Escherichia coli. Ces modifications indiquent une amélioration de la santé intestinale et une réduction de l'inflammation systémique. 4. Corrélations entre cerveau et microbiome : Des corrélations temporelles ont été observées entre les changements du microbiome intestinal et les altérations de l'activité cérébrale. Par exemple, la diminution de l'abondance de E. coli était associée à une réduction de l'activité dans le gyrus frontal inférieur orbital gauche, suggérant une interaction dynamique entre l'intestin et le cerveau pendant la perte de poids. Implications de l'étude Cette recherche met en évidence l'impact du jeûne intermittent sur l'axe cerveau-intestin-microbiome. Les modifications synchronisées de l'activité cérébrale et de la composition microbienne intestinale suggèrent une communication bidirectionnelle influençant la régulation de l'appétit et le métabolisme énergétique. Ces résultats ouvrent des perspectives pour des interventions thérapeutiques ciblant simultanément le cerveau et le microbiome afin de traiter l'obésité et ses complications associées. En conclusion, le jeûne intermittent induit des changements bénéfiques dans le cerveau et le microbiome intestinal, contribuant à une meilleure régulation de l'appétit et à une amélioration des paramètres métaboliques chez les individus obèses. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

In this episode, we explore the crucial role of the protective mucus layer in maintaining intestinal lining integrity, highlighting how it shields the epithelial cells from harmful substances and supports overall digestive function. We dive into the components and functions of mucins, goblet cells, and secretory IgA, explaining their contributions to gut immunity and barrier integrity. Additionally, we discuss strategies for supporting mucus production centered around butyrate, N-acetyl glucosamine, and plant-derived mucilage. Topics: 1. Introduction: Overview of the Gastrointestinal Mucus Layer - Importance of the mucus secretions in forming a protective layer - Brief review of the gastrointestinal lining and its structure 2. The Mucosal Layer and Its Components - The mucus layer on the epithelial cells of the mucosa - Four main layers of the intestinal wall, focusing on the mucosa - Epithelium: absorptive enterocytes and mucus-secreting goblet cells - Lamina propria: connective tissue rich in immune cells, blood vessels, and lymphatics - Smooth muscle aiding in subtle movements - Submucosa: thicker connective tissue layer with blood vessels, nerves, and lymphatics 3. Dual Function of the Mucus Layer - Physical barrier preventing pathogens and toxins from reaching epithelial cells - Biochemical barrier housing antimicrobial peptides and immunoglobulins 4. Goblet Cells and Their Role in Mucin Production - Goblet cells: specialized epithelial cells producing mucins - Distribution of goblet cells from small to large intestine - Importance of goblet cells in maintaining the mucus barrier 5. Mucins: Structure and Glycosylation - Glycosylation and its role in mucus properties and host-microbiota interactions - Commensal bacteria and their interactions with mucins (e.g., Bacteroides and Akkermansia muciniphila) 6. The Importance of Controlled Mucin Degradation - Mutualistic relationship between mucin-degrading bacteria and the host - Risks of dysregulated mucin degradation, leading to dysbiosis and leaky gut 7. Secretory IgA and Its Role in Gut Immunity - Overview of secretory IgA (sIgA) and its production - sIgA's mechanism of neutralizing pathogens "without inflammation" - Immune exclusion as a defense mechanism to maintain gut barrier integrity 8. Recap: The Dynamic Nature of the Mucus Layer - Continuous renewal of the mucus layer and the role of goblet cells and plasma cells - Importance of regular mucus turnover for maintaining a healthy gut barrier 9. Supporting Gastrointestinal Mucus Production - Short-chain fatty acids (SCFAs) and their role in stimulating mucus production - Butyrate and its effects on goblet cells and epithelial repair - N-Acetyl Glucosamine (NAG) as a supplement to support mucin glycosylation 10. Supporting the Intestinal Lining After Dysbiosis or Increased Permeability - Mucilage and its role in coating and soothing mucosal surfaces - Plant-derived mucilage from slippery elm and marshmallow root - Physical protection provided by mucilage - Soothing effects on inflamed tissues and promoting smooth digestion Thank you to our episode sponsor: 1. Check out ⁠⁠⁠Daily Nouri⁠⁠⁠ and use code ⁠⁠⁠CHLOE20⁠⁠⁠ for 20% off your order. Thanks for tuning in! Get Chloe's Book Today! "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to purchase products, subscribe to our mailing list, and more! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

Sono stati resi noti i dati di una ricerca estremamente interessante che collega la vitamina D alla resistenza al cancro attraverso il microbioma intestinale.Ricercatori del Francis Crick Institute hanno scoperto che la vitamina D promuove la crescita di uno specifico tipo di batterio intestinale, Bacteroides fragilis, che migliora l'immunità contro il cancro.

In this episode, we review the high-yield topic of⁠ Bacteroides fragilis⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠from the Microbiology section. Follow ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Medbullets⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbull --- Send in a voice message: https://podcasters.spotify.com/pod/show/medbulletsstep1/message

Frequently in my practice, in addition to dealing with cases related to breast implant illness, I encounter patients experiencing gastrointestinal issues. That is why it's vital to shed light on the complex interplay between breast health and gut health, prompting a comprehensive approach to address the multifaceted nature of these health concerns. Addressing issues in the gut is crucial as it significantly impacts gut health and overall well-being. This episode focuses on actionable steps for individuals seeking to optimize their gut health. Diet and supplements for gut health and inflammation Sometimes, despite the efforts of disciplined or diligent individuals following a clean diet to support their well-being, certain challenges still arise. This is due to contributing factors such as probiotic intake and water choices. I often advise patients to reconsider the pH balance of their water and to opt for filtered water instead. Lemon water, praised for its potential to eliminate harmful bacteria due to its acidity, can lead to imbalances when consumed excessively over time. The acidity of lemon water, while potentially beneficial in targeting specific bacteria such as E. coli, Bacteroides fragilis, and fungi, requires a delicate balance. Prolonged and excessive consumption of lemon water can disrupt this equilibrium, resulting in unintended consequences for the microbiome. Understanding the implications of these hormonal dynamics becomes pivotal in devising effective strategies for managing menstrual health. In the context of pre-menopausal women grappling with cycle-related challenges such as pain, excessive bleeding, polycystic ovary syndrome (PCOS), or endometriosis, elevated estrogen levels and impaired estrogen metabolism emerge as critical areas. Recognizing the complex interplay within the body, I've taken the initiative to create an inflammation support bundle that addresses the multifaceted nature of health challenges. This specially curated bundle places a significant emphasis on incorporating liposomal versions of key components for optimal absorption. By integrating this bundle into your daily health routine, you can take a proactive step toward mitigating inflammation and promoting overall well-being. Grab yours now: https://drrobssolutions.com/ Managing gut health issues concerning breast implant illness through dietary changes and supplements In our clinic, we've encountered challenges with anemia, especially in patients with gastrointestinal issues. Anemia, exacerbated by fatigue, can reach a point where ferritin levels necessitate iron transfusions, a situation we've addressed in our practice, especially before surgical procedures. To normalize symptoms like anemia, gastrointestinal distress – including constipation, diarrhea, bloating, and swelling – I recommend simple interventions such as switching to filtered water and temporarily discontinuing probiotic use. For those diligently pursuing a nutrient-dense diet, particularly with higher protein intake, I recognize the challenges the body may face in breaking down these nutrients. In these instances, incorporating additional digestive enzymes, such as MassZymes from BIOptimizers, can be an effective solution to enhance digestion and nutrient absorption. However, when dealing with complex cases, we do a more holistic approach involving a thorough examination of the patient's genetics, a toxicity profile, and a comprehensive assessment using tools like a GI map, which includes a stool test, food sensitivity tests, and hormone evaluations. This approach allows for a clearer understanding of the patient's overall health, especially when dealing with extreme gut problems, digestion issues, and persistent symptoms like swelling, bloating, and pain. Remember, prioritizing gut health is paramount, especially before undergoing surgery, a consideration often overlooked but crucial in the journey to overcoming breast implant illness. Check out our Inflammation Support Bundle, a comprehensive resource tailored to guide individuals on their paths to better gut health, recognizing the pivotal role it plays in mood, immune function, and overall vitality. About Dr. Rob: Austin's natural plastic surgeon Dr. Robert Whitfield brings you the true stories of actual patients, navigates through their surgical and non-surgical treatment options, then reveals their chosen path forward and the results they achieved. Dr. Rob is a board certified plastic surgeon and Austin's Natural Choice for plastic surgery, laser and energy treatments, and aesthetics. Links and Resources Dr. Robert Whitfield's Website (https://drrobssolutions.com/) Follow Dr. Rob on Instagram https://www.instagram.com/drrobertwhitfield/ For more information on Virtual and In Person Consultations, we always answer our messenger personally: https://www.drrobertwhitfield.com/contact/

If you want to improve your digestion, your immune system, and your overall health, one might begin with a focus on a healthy gut microbiome. Today we're talking with Stanford University professor of microbiology and immunology Dr. Justin Sonnenburg, co-author of the book entitled, "The Good Gut: Taking Control of Your Weight, your Mood, and Your Long-Term Health." He and his wife, research scientists Dr. Erica Sonnenburg, argue that our typical modern diet has caused the microbial diversity or intestine to shrink substantially. Turns out that's a big problem. Interview Summary My impression is that this field of work on the microbiome is just exploding. It seems like every day something new comes out, something exciting, some kind of major breakthrough. It's wonderful to have a leading scientist like you to join us to help explain this. Let me begin with this question. I recently read something very interesting in the article that discussed your work, namely that you've hypothesized, and this is a quote from this article, "Humans may merely be elaborate vessels "designed for the propagation of bacterial colonies." Now that's pretty interesting. Tell us more if you would? Yes, absolutely. I should note that this is an idea that has been propagated, just as microbes are propagated over time. I did say that, but I'm now attributing it to the great scientists that came before me. I will say that the microbes in our gut have been for a long time a curiosity. For hundreds of years we've known that they live there. Over time we've learned that they're affected by what we eat. We know that they're involved in digestion and gut health. But what is really phenomenal is, as you alluded to in the introduction just the ability of these microbes to impact so many dimensions of our health. Everything from our immune system, to metabolism, to things like moods, behavior, and neurodegeneration. When you start to think about microbes getting passed from generation to generation - because as a new baby is born, their gut is sterile in the womb, and then they're rapidly colonized when they come to this world largely by microbes from their mother and other adults around them - you start to realize that these microbes may actually be the ones calling the shots and dictating aspects of our biology to promote their growth through evolutionary time. It does change the way you think about this relationship in some ways. One might jump to the conclusion that microbes are a bad thing, and you'd like to have fewer of them. That's in fact what antibiotics do, they get rid of them. But we need more rather than less, and it sounds like the shrinking diversity of the microbiome is really a problem. How do our diet and lifestyles damage the vitality of the human microbiome? I'm imagining this is a 'let me count the ways question,' but what are the leading concerns in your mind? Yes, completely. I think you're right in that it's very hard to single out one particular factor, because as populations become more industrialized and embrace all of the technologies and medical practices that go along with the industrialized lifestyle, we have so many factors that can impact our microbiome. Certainly, diet is a major factor, and we can come back to this. But we know that most of the microbes in our gut reside at the far reaches of our digestive tract - at the very end of the line down in our colon in our large intestine. That means that if we're eating simple nutrients, like most of the things in a western diet - sugars, starch, fat, protein - a lot of those things get digested and absorbed in our small intestine, which leaves nothing remaining for the microbiota. It's really complex carbohydrates and dietary fiber, that serve as the major fuel for the microbiota because we can't digest those complex carbohydrates. The western diet has greatly reduced dietary fiber content, which has left a lot of our gut microbes starving. But there are other aspects of diet, certainly artificial sweeteners, emulsifiers, and probably the high fat content of the western diet are not great for our microbiome. Then beyond diet, antibiotics as you mentioned known to be great for fighting infectious diseases, but not so great for maintaining all of the friendly microbes that we harbor in our body. A variety of other factors like C-sections, baby formula, the incredible sanitation in our environment, again, a lot of these things are a trade-off because we have reaped a lot of benefits from a lot of the lifestyle medical practices technologies. But at the same time, we've implemented these in the absence of understanding the importance of our gut commensals, and the other commensals on our body for our health. Now we really need to start thinking about do we need to restore diversity to this community? Certainly, we need to start thinking about taking care of the community more diligently. You mentioned in some detail how diet affects the gut, but how does it happen in the reverse? Is there a reciprocal relationship going on? Yes, it's a great question, and there are some papers that have been published looking at how gut microbes can affect food choice in model organisms like fruit flies and other organisms that are studied in the lab. We know that microbes in the gut as they metabolize things are producing a lot of interesting chemicals, little metabolites that get absorbed into our bloodstream can circulate through our body. Certainly, some of them cross the blood-brain barrier and can interact with our central nervous system. Now, whether some of those molecules can actually impact our food choice, I think is an interesting topic, we don't know a lot about that. You can imagine a microbe that's really good at, for instance, degrading pectin and it might grow very well. We know there are many microbes that grow well when we, for instance, eat an apple. If that microbe happens to produce a molecule just by chance that then can go in and increase our craving for an apple, that microbe has hit the jackpot for proliferating, it can guide our actions to choose an apple and then it actually profits from the pectin that comes in when we eat the apple. While this would be a very rare quirky event to happen, when you think about the trillions of microbes that exist in every person and have existed in every person across the planet throughout time. It's possible that things like this have happened, and it's a matter of us as scientists trying to track down those stories. There's at least some optimism that there could be virtuous cycles that gets set up rather than these destructive cycles potentially. Help us place this in some sort of a context. You talked about a myriad of dietary things that could affect the microbiome, and probably other things out there in the world too. How serious is the impact? Yes, and this brings up kind of the question of what is a healthy microbiome? Has lifestyle impact that our microbiome? What would be ideal would be to have a time machine to go back, and actually survey what the microbiome looked like thousands of years ago before industrialization, and maybe even going back greater than 10,000 years to what our gut microbiome looked like when we were hunter-gatherers even before we started farming. Just to get a sense of what are the microbes that humans harbored over long periods of time during our evolution with the idea that perhaps our human genome was shaped over evolutionary time in some way by these microbes, that we have adapted our human biology to deal with the specific set of microbiome features or species. We don't have a time machine, but there have been groups that have surveyed paleo feces for instance - the fossilized stool from humans from 1 to 2000 years ago. These data indicate that the microbiome has changed drastically. As we have industrialized, we have totally departed from this more ancestral microbiome. The other way that we can gain insight into this is by looking at modern humans that live lifestyles similar to our ancestors. Hunter-gatherer populations and rural agriculturalists, and we've done a lot of work studying the Hadza hunter-gatherers of Tanzania looking at their gut microbiome. That exactly supports what the paleo feces have told us. That there were features in the microbiome from before industrialization that have changed drastically. We've lost species, they've gone extinct. Hunter-gatherers and many rural populations still harbor these microbes. We expect that there's probably around 500 to 1000 different species of bacteria in an individual's gut microbiome. We've lost hundreds of these species over the course of industrialization. Then, the flip side of that is hundreds of other species have come in and replaced them. We've actually had this kind of wholesale change in configuration in our gut microbiome, and what this means to our biology, we're trying to figure out right now, but it is a really marked change. I have to say I admire the breadth of your work all the way from basic laboratory studies to in the field studies with hunter-gatherers. I could see how your big picture view of this is really pretty unique. Let's talk about how the gut communicates with the brain, and does the health of the microbiome affect things like eating regulation? We've talked about that a little bit already, but also things like mental health. I just want to start by saying that this is a field of research that is in very early days still, we have a lot of work to do to really figure out the connections. You can imagine then the gut microbiome composed of hundreds of species, and then trillions of cells and changing over time within an individual, and different between individuals, and then secreting thousands of chemicals that go into the bloodstream. Then put on top of that the complexity of the central nervous system and brain, and then try to map the interactions between the microbiome and the central nervous system is exceedingly complex.  I think that one of the really important things to note here is that if you look at a lot of the anxiety, and depression, Alzheimer's disease, neurodegeneration in general at this center of a lot of these diseases much like other diseases of the industrialized world lies inflammation. The immune system actually becoming too inflammatory, and that leading to, you know, in some cases autoimmune diseases, but in other cases Alzheimer's disease, and/or anxiety and depression. One of the things that our lab is focused on is really trying to understand how when you change the gut microbiome, how does the immune system change? How does the inflammatory status change of the system? Because we really think that this is the key mediator of many of the things that have gone wrong including things like diabetes and metabolic syndrome.  We're now at the point of understanding that certainly if you go into an animal model and you change the gut microbiome in a major way like industrialization has changed the microbiome of people living in the United States, you completely change how the immune system functions. You can really change how an individual would react to a respiratory infection, how well they would respond to an immunotherapy if they were battling cancer, you can just completely change immune system functionality. In trying to understand this better we've started to do dietary interventions in people to see if we change the gut microbiome in beneficial ways with diet, can we make the immune system less inflammatory? We've done this so far in healthy adults, and now we're really interested in extending this into all sorts of populations that are suffering from different inflammatory diseases, including things like anxiety, and depression, and neurodegenerative diseases. We'll have more information about this. There's some beautiful fundamental research out there that shows unequivocally that the gut microbiome is regulating behaviors, and cognition, and fundamental aspects of what happens in our brain. But a lot of this has been done in animal models, and it's very hard to extend to humans in a detailed way. I can't wait to see these studies, they're just absolutely fascinating and so important. You know, something occurred to me as I was thinking about this, and this may be outside the area of work that you're focused on, but there's a lot of interest out there in the world and the impact of endocrine disrupting chemicals, or things that leach from plastics and things known as forever chemicals, and their impacts on a whole host of things like cancers, and obesity, diabetes and more. Is there any reason to worry about the microbiome in this context? Yes, completely. I think everything that we come in contact with, particularly things that we ingest, but even things that are absorbed through our skin or we inhale, the microbes that live in and on us are just incredibly sensitive detectors of everything going on in the environment. I mean, their survival depends upon it. One of the, in fact, key features of one of the first species from the gut microbiome to have its genome sequenced, Bacteroides thetaiotaomicron this is a bacterial species that was sequenced in the lab of Jeffrey Gordon, it was published in 2003. One of the key interesting features of that genome was the expansion of environmental sensors that were encoded by that genome. It was very clear that this bacterium was living in a dynamic environment, and having to sense and respond to minute to minute variations in the chemical cues that were coming in. That means that when you start to change those chemical cues, you start to change the function of the microbiome because those sensors that those bacterial encode are wired into their function and how they behave. This is again, hypothesis, but I think your question is a a great one because there are these realms of inquiry where we are just right at the beginning of understanding that major things that are going on in our environment could be impacting this really essential component of our biology. And we really have no specific idea of how the perturbations may cascade through our microbiome and our biology. A lot to look at there, but I have no doubt that those chemicals are having an impact on this community filled with environmental sensors. It's going to be so interesting to see that work take shape. It would be great if community of people working on the microbiome could come together with the people in interested in the impact of these forever chemicals on health so that a full picture of their impact can get painted. So what do you think are the most pressing scientific questions that need to get addressed? I think that we're still really searching for the definition of a healthy microbiome. And this is something that dates back to a wonderful project that was started by the National Institutes of Health, the Human Microbiome Project. That was an effort from sequencing centers that had sequenced the human genome to turn these sequencing technologies to this uncharted aspect of our human biology, our microbiome. One of the goals of that sequencing project was to determine what a healthy gut microbiome is. And our assumption at the time was, well, we should sequence a bunch of healthy Americans, and kind of look at what's common between them. We now understand that the healthy American most likely harbors a microbiome that is not really optimal for health, it's actually probably a microbiome that's predisposing us to a number of inflammatory conditions.   Our human genome probably dictates whether you as a person will get an autoimmune disease, or cancer or you know, a different inflammatory disease. But it's really a microbiome that appears to be pro-inflammatory, and so that doesn't mean that it's terrible and that we need to scrap the whole thing. But it means that it probably can be improved. A big part of that improvement probably can come through feeding it better food and getting better functionality out of the microbes we have. But it also probably means that we need to bring back certain functions or certain species that we've lost over the course of industrialization, to bring back some of that biodiversity.  You know, I think of the microbiome as similar to this complex rainforest, just hundreds of species interacting in this really dynamic way, and as you start to degrade that ecosystem it's really hard to maintain its full functionality. You start to lose functions, and it starts to operate suboptimally. And so thinking about ways to bring back the health and biodiversity of this ecosystem, I think is super important. One of the key things that we have to do as a field, and I want to just reflect back on the work that we're doing with hunter-gatherers and implications for what might be a healthy microbiome. It is not at all clear that all of the microbes that we've lost are healthy and need to be reinstalled in our gut. I think that we've probably lost species that we, you know, just as soon not have. But mapping which ones are health-promoting, and in which context, because you know, what's health-promoting for one person may not necessarily be health promoting for someone else that's going through something very different in their life in a different life phase. So we need to understand all that complexity, and really crystallize how can we optimize a microbiome for an individual in a given context.  This sounds like a really complex problem, and it is, but I think that one of the really exciting things that's happening in the field right now is this combination of what we call omics data, the ability to measure so many different aspects of the microbiome at one time so we can get a really detailed picture. Then all the great computational approaches for bringing all that data together, using things like machine learning and artificial intelligence on big data sets to really distill out meaningful signals that give us a better idea of some of these complex questions. It is a complex thing to go after, but I think it's not out of reach and that's I think the big frontier for the gut microbiome. Well, speaking of the big frontier, let's end with a big picture question. What can be done to make things better? You mentioned improving diet would be one thing, but how do you look at those big picture questions? One of the incredible things about the gut microbiome and its relationship to its human host, is this like feedback system. For instance, if you are in a slightly inflammatory state, it can be hard to get out of that inflammatory state because the inflammation is reinforcing microbes that are then reinforcing the inflammation. You end up with these feedback loops that are very hard to break, so even if you were to do something like a fecal transplant in some instances of inflammation where you try to reinstall healthy microbes, those may not engraft and take up residence because the host inflammation will get rid of the good microbes and select in the microbes that feed the inflammation. There are these feedback loops that are very hard to break, and we know the gut microbiome is very resilient, so you can perturb it and it will by and large return to a starting state, not exactly what the starting state was, but there is this great resilience and recalcitrant to change over short time periods. This is why industrialization has been so powerful because it's happened over multiple generations across an entire population, and it's driven our microbiome in one direction.  I think if we want to bring back a more diverse healthy microbiome, it requires changes in our habits, changes in what we eat day after day for years on end to really change the species that are in our microbiome and what those species are doing. We got a little bit of insight into this, but I'll finish with one specific example. One of the dietary interventions that we did, we compared a high fiber diet, so this is eating things like legumes, whole grains, vegetables, fruits, thinking that that would be kind of optimal food for a healthy gut microbiome. We compared that diet with a high fermented food diet, so another cohort of individuals, we gave kombucha, kefir, yogurt, kimchi sauerkraut, food with living microbes in it that had been transformed by fermentation. Basically, so these were just healthy adults we let them eat those foods, they ramped up on the foods for four weeks, and then for six weeks they maintained high levels of those foods. We actually saw that the high fiber diet had very different effects on individuals depending upon their starting microbiome. If you had a very diverse microbiome to start with, you actually improved your inflammatory status, you got less inflammatory over the course of the intervention. But if you start with a low diversity microbiome, the high fiber diet doesn't do much for you. The fermented foods actually had a really amazing effect, they increased microbiome diversity and they also decreased over two dozen inflammatory markers that we were able to survey through these great technologies that give us comprehensive immune profiling. We really saw a signature of exactly what we'd want to see to counter the industrialized deterioration of the gut microbiome with the fermented food diet, increased microbiome diversity, decreased inflammation, and this was just over the course of a 6 to 10 week intervention. We're really curious to pursue these findings in more detail, and see if now we can go into diseases that are pro-inflammatory, and counter those diseases to actually treat them in some way with the fermented food diet.  If I were to tell people what to do to counter all the negative impact of industrialization on our microbiome, I would say consume some fermented foods every day, and then start to integrate dietary fiber. As you eat the fermented foods, you'll increase your microbiome diversity. And our hope is that will allow you to harness the benefit of the high fiber diet as your microbiome diversity increases. Bio Justin Sonnenburg is a professor of microbiology and immunology at Sanford University. His research focuses on the basic principles that govern interactions within the intestinal microbiota and between the microbiota and the host. He is the coauthor of The Good Gut: Taking Control of your Weight, Your mood, and Your Long-Term Health.  

Today, I am blessed to have here with me Dr. Shayne Morris. He has unique and broad experiences, for over 30 years, in the nutritional industry and scientific community. Trained first in the ways of natural product sourcing, quality, design and manufacturing which, quickly led to the pursuit of a formal education in chemistry, microbiology, and finally a Ph.D. in molecular biology and biochemistry. Passionate about owning a business in the industry, Dr. Shayne Morris also earned a Master's in Business degree. He is an adjunct professor in chemistry at WSU and is a Certified Nutrition Specialist in the American College of Nutrition. Dr. Shayne Morris has authored a number of peer-reviewed journal articles, scientific abstracts, talks and patents in the areas of biological chemistry, natural products and product development. Recent significant research is focused on our microbiome and the probiotic potential of unique human microbes. As part of Dr. Shayne Morris' research his lab has developed unique growing and stabilizing methods for important commensal organisms like Bacteroides, Akkermansia, beneficial phage and more. Not only are personalized microbes important the nature of their food and metabolites are equally important to the microbiome as a whole and the human symbiosis. Therefore, prebiotic research has become an inseparable component of the probiotic research and in some cases more impactful than probiotics alone. In this episode, Dr. Shayne Morris opens the show by discussing how he became invested in the microbiome. Ketosis is fantastic for the microbiome; Dr. Morris explains what benefits are taking place in the gut when you're burning ketones. We have 10 trillion cells in the human body, and each has its own job; Dr. Morris reveals how you can help your cells complete their job as efficiently as possible. Tune in as we chat about your microbiome's circadian rhythm, the importance of bile, and Systemic Formulas. Get Systemic Formulas Supplements here: http://www.ketokampsupplements.com  90 Day Detox Program: http://www.ketokampdetox.com Order Keto Flex: http://www.ketoflexbook.com -------------------------------------------------------- / / E P I S O D E   S P ON S O R S  PureForm Omega Plant Based Oils (Best Alternative to Fish Oil): http://www.purelifescience.com Use ben4 for $4.00 off. EveryDay Dose Everything you love about coffee, none of what you don't — say goodbye to jitters, anxiety, crash, and digestive issues. https://everydaydose.superfiliate.com/KETOKAMP  (5 FREE Travel Packs + Free Frother applied) Text me the words "Podcast" +1 (786) 364-5002 to be added to my contacts list.  [01:10] How Dr. Shayne Morris Got Involved In The Health Space When Dr. Morris got into the health space, there was very little hard science on the miraculous nature of how herbs work. To learn more, Dr. Morris buried himself into the educational side and went after microbiological degrees along with biochemical degrees. It wasn't until the 2000s that we identified the importance of microbes. Remember, we're a human built from about 10 trillion cells. Now, Dr. Morris has a research lab on the microbiome and develops products to improve the microbiome. [08:50] Why Dr. Shayne Morris Is Such A Big Fan of Keto One of the most brilliant aspects of adapting to keto is for people that are struggling with metabolic issues. Every organ in the body can utilize ketones. Ketones can really change the way that mitochondria work. Plus, ketones can affect the oxidative stress that cells are under. On a cellular level, ketones offer so much benefit in terms of their energy production. Lastly, we're genetically predesigned to store fats. [17:20] We Have 10 Trillion Cells, and Each Cell Has Its Own Job We are a complex of 10 trillion cells. Each cell has its own job. For instance, the cells in the eye behave very differently than the cells in the brain. Each and every one of those cells has a very specific set of duties. For a cell to do its job, it needs energy! Overall, we want to generate more positive genetic outcomes on the cellular level. [24:40] How Your Gut Affects Your Whole Body There's a complexity of color that we see in nature. When you eat different compounds, you are feeding the microbiome. We have to think about the microbiome as the gateway to all the things we need in our bodies. Our gut, anatomically, is the largest immune system. Plus, it is the largest innervated system outside of the brain. The gut controls everything. Your microbiome is what's directing all of the traffic in the body. [30:15] Why Burning Sugar Is Producing More Cellular Inflammation When you look at burning sugar, there's a time and a place. Burning sugar is a quick way to release energy. When you eat sugar, it should come from plants. Sugar and flour are not good sources of carbs. Burning sugar can generate free radicals. When you're flooding the mitochondria with just sugar, it gets overwhelmed. All these signals are going out into the cell, saying we're broken, and it's time to shut down. [40:25] Do You Really Need To Eat Vegetables? Your microbiome has a circadian rhythm. That rhythm isn't just based on the moon or the sun; it's based on the nutrients we get. If we're in winter, we have a different microbial rhythm than we do in the summer. These rhythms are part of the more, the greater picture of diet. Throughout the winter, there typically weren't fruits and vegetables to eat. Instead, people would eat fats and meats. Our microbiome is supremely adapted to function on these rhythms and on these different diets. When you rotate your diet, it creates diversity. [59:00] Learn More About Systemic Formulas: Lb – Liver/Gall Bladder Check out Lb here: https://revelationhealth.com/products/systemic-formulas-61-lb-liver-gall-bladder?_pos=2&_sid=a6614201f&_ss=r/azadi?afmc=azadi This formula was designed to help the body maintain proper portal duct function. It assists in purifying the blood of mucus-forming matter. There are a number of herbs that we know can drive up bile production. Plus, all these mechanisms or pathways that help us produce those so you can generate enough bile. If you take enzymes, they help break down the lipids, the carbohydrates, and the proteins. Probiotics and prebiotics will drive up the quality and quantity of bile needed to address healthy fats. AND MUCH MORE! Resources from this episode: Check out Dr. Shayne's Website: https://drshaynemorris.com/ My Byome: https://mybyome.com/ Learn more about Systemic Formulas: https://systemicformulas.com/ Follow Dr. Shayne Morris Instagram: https://www.instagram.com/drshaynemorris/ Facebook: https://www.facebook.com/drshaynemorris/ YouTube: https://www.youtube.com/channel/UCTOm0SSKJulize06GMzEM-A Check out Terra: https://revelationhealth.com/products/mybiome-terra-byome-60-caps/azadi?afmc=azadi Get Lb here: https://revelationhealth.com/products/systemic-formulas-61-lb-liver-gall-bladder?_pos=2&_sid=a6614201f&_ss=r/azadi?afmc=azadi Learn more about Immuno Pre-Byome: https://revelationhealth.com/products/mybiome-367-neuro-prebyome-300g/azadi?afmc=azadi Keto Kamp Supplements: http://ketokampsupplements.com/ Join theKeto Kamp Academy: https://ketokampacademy.com/7-day-trial-a WatchKeto Kamp on YouTube: https://www.youtube.com/channel/UCUh_MOM621MvpW_HLtfkLyQ 90 Day Detox Program: http://www.ketokampdetox.com Order Keto Flex: http://www.ketoflexbook.com -------------------------------------------------------- / / E P I S O D E   S P ON S O R S  PureForm Omega Plant Based Oils (Best Alternative to Fish Oil): http://www.purelifescience.com Use ben4 for $4.00 off. EveryDay Dose Everything you love about coffee, none of what you don't — say goodbye to jitters, anxiety, crash, and digestive issues. https://everydaydose.superfiliate.com/KETOKAMP  (5 FREE Travel Packs + Free Frother applied) Text me the words "Podcast" +1 (786) 364-5002 to be added to my contacts list.  *Some Links Are Affiliates* // F O L L O W ▸ instagram | @thebenazadi | http://bit.ly/2B1NXKW ▸ facebook | /thebenazadi | http://bit.ly/2BVvvW6 ▸ twitter | @thebenazadi http://bit.ly/2USE0so ▸clubhouse | @thebenazadi Disclaimer: This podcast is for information purposes only. Statements and views expressed on this podcast are not medical advice. This podcast including Ben Azadi disclaim responsibility from any possible adverse effects from the use of information contained herein. Opinions of guests are their own, and this podcast does not accept responsibility of statements made by guests. This podcast does not make any representations or warranties about guests qualifications or credibility. Individuals on this podcast may have a direct or non-direct interest in products or services referred to herein. If you think you have a medical problem, consult a licensed physician.

On episode #27 of the Infectious Disease Puscast, Daniel and Sara review the infectious disease literature for the previous two weeks, 4/13 – 4/25/23. Hosts: Daniel Griffin and Sara Dong Click arrow to play Download Puscast 027 (19 MB .mp3, 31 min) Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of Puscast! Links for this episode Prevalence, clinical severity, and seasonality of Adenovirus 40/41, Astrovirus, Sapovirus, and Rotavirus among children with moderate-to severe diarrhea (CID) Antibiotic-prescribing practices for management of childhood diarrhea in 3 sub-Saharan African countries (CID) Drivers of decline in diarrhea mortality (CID) Breastfeeding among people with HIV in North America (CID) Wearable sensor-based detection of Influenza in presymptomatic and asymptomatic individuals (JID) Emergence of erythromycin-resistant invasive group a Streptococcus (EID) Piperacillin-Tazobactam compared With Cefoxitin as antimicrobial prophylaxis for pancreatoduodenectomy (JAMA) VE303 for prevention of recurrent Clostridioides difficile infection (JAMA) Geographic patterns of antimicrobial susceptibilities for Bacteroides species worldwide (IJAA) Intravenous to oral antibiotic switch therapy among patients hospitalized with community-acquired pneumonia (CID) Clinical impact of syndromic molecular point-of-care testing for gastrointestinal pathogens in adults hospitalized with suspected gastroenteritis (The Lancet) Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin B (Mycoses) Giardia detection and codetection with other enteric pathogens in children in the vaccine impact on diarrhea in Africa (CID) Feasibility of training community health workers to use smartphone-attached microscopy for point-of-care visualization of soil-transmitted helminths (AJTMH) Compassionate use of bacteriophages for failed persistent infections (OFID) Music is by Ronald Jenkees

Co-hosts Dr. Tania Cubitt and Katy Starr discuss leaky gut syndrome in horses, including the type of horses that are more at risk, symptoms, causes and treatment for leaky gut and management tips to implement to prevent leaky gut from developing in horses.____________________________________Notable References:1:00 – Gastrointestinal issues are reported second to only old age as the leading cause of death in horses- https://www.standleeforage.com/standlee-barn-bulletin/leaky-gut-syndrome-in-horses/4:00 – For visuals of the villi and intestinal permeability Dr. Cubitt and Katy mention, visit this research manuscript - https://pubmed.ncbi.nlm.nih.gov/9622321/30:44 – Rate and review the Beyond the Barn podcast on Apple here - https://podcasts.apple.com/.../beyond-the-barn/id154122130630:44 –Rate the Beyond the Barn podcast on Spotify here – https://open.spotify.com/show/3dmftQmwLKDQNueUcCJBZa____________________________________Love the podcast? Leave a rating and review on Apple – https://podcasts.apple.com/.../beyond-the-barn/id1541221306Leave a rating on Spotify – https://open.spotify.com/show/3dmftQmwLKDQNueUcCJBZaHave a topic idea or feedback to share? We want to connect with you! Email podcast@standlee.comShare our podcast and learn more about our co-hosts at our Beyond the Barn podcast pageSUBSCRIBE to the Beyond the Barn podcast email to be an exclusive insider!Find us on Apple, Spotify or Google Podcasts and SUBSCRIBE, so you never miss an episode.____________________________________Check out the Standlee Barn Bulletin BlogFind more nutritional resources from Dr. Stephen Duren and Dr. Tania Cubitt at https://www.standleeforage.com/nutrition/nutritional-resourcesConnect with Standlee on Facebook, Instagram, YouTube and TikTok____________________________________*Views and opinions expressed by guests are their own and do not necessarily reflect the view of Standlee Premium Products, LLC.*

Episode 130: Epigenetics in childhood obesitySaakshi and Dr. Arreaza discuss some principles of epigenetics implicated in the development of obesity in children. Written by Saakshi Dulani, MS3, Western University College of Osteopathic Medicine of the Pacific. Edited by Hector Arreaza, MD.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.This topic is constantly expanding, and I'm excited to talk about it. It is a fact that epigenetic changes play a role in the development of certain diseases such as Prader-Willi syndrome, Fragile X syndrome, and various cancers. It has been demonstrated that certain foods can alter gene expression in animals, for example. What is epigenetics?Epigenetics is the regulation of gene expression without a change in the base sequence of DNA. Epigenetics means “on top of” the genes. Genes can be turned “on” or “off” as a response to external influences. Obesity and Epigenetics.The link between genetics and obesity is complex, but it is known that epigenetics plays a significant role in childhood obesity. Surprisingly, exposure to environmental factors starts in the uterus. Fetuses are exposed to intrauterine signals that increase their potential to develop obesity. Factors such as in-utero hyperglycemia, gestational diabetes mellitus, and early childhood diet and lifestyle practices can affect the development of the gut microbiome, modify gene expression through DNA methylation, and increase the risk of childhood obesity. These gene expression changes can be passed on to future generations. DNA methylation is the addition of a methyl group to part of the DNA molecule. That methyl group acts as a “chemical cap,” which prevents gene expression. Another example of epigenetics is histone modification. Histones are proteins that are used by DNA as spools to wrap around pieces of information that are “not needed”. The reason why a scalp cell and a neuron are different is that the expression of certain genes is suppressed while other genes are expressed.Factors that influence obesity.Some factors that increase the risk of childhood obesity through epigenetic changes include neonatal intestinal microbiome, C-section delivery, maternal insulin resistance, exposure to antibiotics and other environmental toxins, early introduction of complementary foods, parental diets high in carbohydrates and low in fruits and vegetables, and poor sleep. There are many other factors, but we will discuss only a few of them.Microbiome:The microbiome is a whole new world that is being explored by many investigators. The gut microbiome refers to the diverse community of organisms, including bacteria, fungi, and viruses, that reside in the human intestine. The neonatal intestinal microbiome is established during the first two years of life and may be influenced by factors such as the method of delivery, maternal obesity, and the maternal gut microbiome. Some bacteria worth mentioning are Bacteroides, Clostridium, and Staphylococcus. These gut bacteria are higher in pregnant women who have obesity, and they also have a low count of Bifidobacterium. Infants born to obese mothers have higher levels of bacteria associated with increased energy harvest compared to infants born to normal-weight mothers. The gut microbiome of infants delivered by C-section is different than infants delivered vaginally.Link to antibiotics:Early exposure to antibiotics is associated with the development of resistance in microorganisms. The intestinal microbiota exposed to antibiotics also shows reduced diversity. Antibiotics can decrease the number of mitochondria and impair their function, which is important in maintaining energy metabolism. Evidence suggests that some antibiotics can cause mutations in the mitochondrial genome, and they have a direct effect on the microbiome and influence metabolism. There is a strong association between early-life antibiotic exposure and childhood adiposity, with a strong dose-response relationship. A stronger association has been seen with exposure to broad-spectrum antibiotics and macrolides. Maternal insulin resistance (IR):Insulin resistance means that the mother needs levels of insulin that are higher than normal to stay normoglycemic. It means the insulin receptors are “exhausted” and do not respond to normal levels of insulin. Insulin does NOT cross the blood-placenta barrier, but glucose and other nutrients do. This causes the fetus to have an abundance of glucose that stimulates the secretion of high levels of insulin by the fetal pancreas to stay normoglycemic. The combination of insulin + glucose is the perfect combination for anabolism, adipocyte hyperplasia, and fetal growth. That explains why mothers with insulin resistance deliver larger babies (macrosomia). Maternal insulin resistance is a predictor of infant weight gain and body fat in the first year of life. This is not influenced by the mother's BMI before pregnancy. Maternal insulin resistance causes alterations in gene regulation for lipids, amino acids, and inflammation, leading to long-term health implications for both the mother and future pregnancies.C-section and obesity:C-section delivery is a saving procedure for many obstetrical emergencies. C-sections have improved the survival of larger infants and their mothers. C-sections are more frequent among populations with obesity and sedentary lifestyles. This method of delivery is also strongly associated with childhood obesity. Among many other reasons, whenever a vaginal delivery is feasible, a vaginal delivery is preferred over a c-section.   In summary, we discussed 4 factors that may influence childhood obesity: the newborn microbiome, exposure to antibiotics, maternal insulin resistance, and C-sections. There are many other factors that we did not talk about, but the more we know about genetics, epigenetics, and metabolism, the closer we get to a better understanding of obesity._____________________Conclusion: Now we conclude our episode number 130, “Epigenetics in childhood obesity.” Saakshi discussed with Dr. Arreaza that the in-utero environment can alter gene expression and increase the risk of obesity in children. Some factors, such as maternal insulin resistance and changes in gut microbiome, can be the cause of obesity in some children. This week we thank Hector Arreaza and Saakshi Dulani. Audio editing by Adrianne Silva.Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! _____________________Sources:Burdge GC, Hoile SP, Uller T, Thomas NA, Gluckman PD, Hanson MA, Lillycrop KA. Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition. PLoS One. 2011;6(11):e28282. doi: 10.1371/journal.pone.0028282. Epub 2011 Nov 30. PMID: 22140567; PMCID: PMC3227644. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227644/Rachael Rettner, Epigenetics: Definition & Examples, Live Science, published on June 24, 2013, available at: https://www.livescience.com/37703-epigenetics.htmlMulligan CM, Friedman JE. Maternal modifiers of the infant gut microbiota: metabolic consequences. J Endocrinol. 2017;235: R1-R12.Aghaali, M. and S. S. Hashemi-Nazari (2019). “Association between early antibiotic exposure and risk of childhood weight gain and obesity: a systematic review and meta-analysis.” J Pediatr Endocrinol Metab 32(5): 439-445.Yuan C, Gaskins AJ, Blaine AI, et al. Association between cesarean birth and risk of obesity in offspring in childhood, adolescence, and early adulthood. JAMA Pediatr. 2016;170(11):e162385. doi: 10.1001/jamapediatrics.2016.2385.Royalty-free music used for this episode: “Gushito - Burn Flow." Downloaded on October 13, 2022, from https://www.videvo.net/

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.29.526093v1?rss=1 Authors: Moe, S. M., Biruete, A., Chen, N. X., Metzger, C. E., Srinivasan, S., O'Neill, K., Fallen, P., Fonseca, A. D., Wilson, H. E., Evenepoel, P., Swanson, K. S., de Loor, H., Allen, M. A. Abstract: Background: Dietary fiber is important for a healthy diet, but intake is low in CKD patients and the impact this has on the manifestations of CKD-Mineral Bone Disorder (MBD) is unknown. Methods: The Cy/+ rat with progressive CKD was fed a casein-based diet of 0.7% phosphate with 10% inulin (fermentable fiber) or cellulose (non-fermentable fiber) from 22 weeks to either 30 or 32 weeks of age (~30 and ~15 % of normal kidney function). We assessed CKD-MBD, cecal microbiota, and serum gut-derived uremic toxins. Two-way ANOVA was used to evaluate the effect of age and inulin diet, and their interaction. Results: In CKD animals, dietary inulin led to changes in microbiota alpha and beta diversity at 30 and 32 weeks, with higher relative abundance of several taxa, including Bifidobacterium and Bacteroides, and lower Lactobacillus. Inulin reduced serum levels of gut-derived uremic toxins, phosphate, and parathyroid hormone, but not fibroblast growth factor-23. Dietary inulin decreased aorta and cardiac calcification and reduced left ventricular mass index and cardiac fibrosis. Bone turnover and cortical bone parameters were improved with inulin; however, bone mechanical properties were not altered. Conclusions: The addition of the fermentable fiber inulin to the diet of CKD rats led to changes in the gut microbiota composition, lowered gut-derived uremic toxins, and improved most parameters of CKD-MBD. Future studies should assess this fiber as an additive therapy to other pharmacologic and diet interventions in CKD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Videos: A.I. Is Making it Easier to Kill (You). Here's How. | NYT (10:00) Disturbing simulation shows power, terror of killer robots (7:46) Fear Psychosis and the Cult of Safety – Why are People so Afraid? (13:25)   Peanuts Linked to Lower Breast Cancer Risk Washington University in St. Louis & Harvard University, October 22, 2022 Girls ages 9 to 15 who regularly ate peanut butter or nuts were 39 percent less likely to develop benign breast disease by age 30, according to a new study. Benign breast disease, although noncancerous, increases risk of breast cancer later in life. “These findings suggest that peanut butter could help reduce the risk of breast cancer in women,” says senior author Graham Colditz, professor of surgery at Washington University School of Medicine and associate director for cancer prevention and control at Siteman Cancer Center at Barnes-Jewish Hospital. Published in the journal Breast Cancer Research and Treatment, the findings are based on the health histories of 9,039 US girls enrolled in the Growing Up Today Study . When the study participants were 18 to 30 years old, they reported whether they had been diagnosed with benign breast disease that had been confirmed by breast biopsy. Participants who ate peanut butter or nuts two times each week were 39 percent less likely to have developed benign breast disease than those who never ate them. The study's findings suggest that beans, lentils, soybeans, and corn also may help prevent benign breast disease, but consumption of these foods was much lower in these girls so the evidence was weaker. Past studies have linked peanut butter, nut, and vegetable fat consumption to a lower risk for benign breast disease. However, participants in those studies were asked to recall their high school dietary intakes years later. Perinatal Brain DHA Concentration Has a Lasting Impact on Cognition National Institute on Alcohol Abuse and Alcoholism October 20, 2022 A new study on Proteomics is now available. According to news out of Bethesda, Maryland, research stated, “Premature infants are deprived of prenatal accumulation of brain docosahexaenoic acid [DHA (22: 6n-3)], an omega-3 fatty acid [omega-3 FA (n-3 FA)] important for proper development of cognitive function. The resulting brain DHA deficit can be reversed by omega-3 FA supplementation.” “The objective was to test whether there is a critical period for providing omega-3 FA to correct cognitive deficits caused by developmental omega-3 FA deprivation in mice. Twelve timed-pregnant mice were fed an omega-3 FA-deficient diet containing 0.04% a-linolenic acid, and their offspring were fed the same deficient diet (Def group) or changed to an omega-3 FA-adequate diet containing 3.1% ALA at 3 wk, 2 mo, or 4 mo of age. In parallel, 3 E14 pregnant mice were fed the adequate diet and their offspring were fed the same diet (Adeq group) throughout the experiment. Brain FA composition, learning and memory, and hippocampal synaptic protein expression were evaluated at 6 mo by gas chromatography, the Morris water maze test, and western blot analysis, respectively. Maternal dietary omega-3 FA deprivation decreased DHA by > 50% in the brain of their offspring at 3 wk of age. The Def group showed significantly worse learning and memory at 6 mo than those groups fed the adequate diet. These pups also had decreased hippocampal expression of postsynaptic density protein 95 (43% of Adeq group), Homer protein homolog 1 (21% of Adeq group), and synaptosome-associated protein of 25 kDa (64% of Adeq group). Changing mice to the adequate diet at 3 wk, 2 mo, or 4 mo of age restored brain DHA to the age-matched adequate concentration. However, deficits in hippocampal synaptic protein expression and spatial learning and memory were normalized only when the diet was changed at 3 wk.” The research concluded: “Developmental deprivation of brain DHA by dietary omega-3 FA depletion in mice may have a lasting impact on cognitive function if not corrected at an early age.” At risk for diabetes? Cut the carbs, says new study Tulane University, October 26, 2022 While low-carb diets are often recommended for those being treated for diabetes, little evidence exists on whether eating fewer carbs can impact the blood sugar of those with diabetes or prediabetes who aren't treated by medications. Now, according to new research from Tulane University, a low-carb diet can help those with unmedicated diabetes—and those at risk for diabetes—lower their blood sugar. The study, published in the journal JAMA Network Open, compared two groups: one assigned to a low-carb diet and another that continued with their usual diet. After six months, the low-carb diet group had greater drops in hemoglobin A1c, a marker for blood sugar levels, when compared with the group who ate their usual diet. The low-carbohydrate diet group also lost weight and had lower fasting glucose levels. “The key message is that a low-carbohydrate diet, if maintained, might be a useful approach for preventing and treating Type 2 diabetes, though more research is needed,” said lead author Kirsten Dorans, assistant professor of epidemiology at Tulane University School of Public Health and Tropical Medicine. The study's findings are especially important for those with prediabetes whose A1c levels are higher than normal but below levels that would be classified as diabetes. Approximately 96 million Americans have prediabetes and more than 80% of those with prediabetes are unaware, according to the CDC. Those with prediabetes are at increased risk for Type 2 diabetes, heart attacks or strokes and are usually not taking medications to lower blood sugar levels, making a healthy diet more crucial. How early fears play a role in future anxiety, depression University of Texas at Dallas, October 26, 2022 A recent imaging study led by a scientist at The University of Texas at Dallas has identified early risk factors linked to children's temperament and a neural process that could foretell whether an individual might develop depression and anxiety in adolescence and early adulthood. The study, published Oct. 26 in JAMA Psychiatry, tracked a cohort of 165 individuals from 4 months old, between 1989 and 1993, through age 26. Dr. Alva Tang, assistant professor of psychology in the School of Behavioral and Brain Sciences and corresponding author of the study, found that people who are more inhibited in early childhood and who also don't respond typically to potential rewards as adolescents are vulnerable to developing depression later in life, more so than anxiety. When babies are exposed to novel objects, people or situations, some react positively and approach them without fear, whereas others respond with wariness or avoidance. This differentiation defines uninhibited versus inhibited behavior. “We know that inhibited children are more likely to have anxiety disorders later, particularly social anxiety, that begins in late childhood to adolescence,” Tang said. “Less has been known about depression, which generally has a later onset, in young adulthood. But we do know that people who have had an anxiety disorder are 50% to 60% more likely to have depression later in life, so inhibited children should have higher risk for depression as well.” The researchers found that the association between inhibition at 14 to 24 months of age and worsening depressive symptoms from ages 15 to 26 was present only among those who also showed blunted activity in the ventral striatum as adolescents. There was no similar association with anxiety. “We found that behavioral inhibition was related to worsening depressive symptoms into adulthood. This supports the assertion that this temperament shows a stronger relation to developing anxiety in adolescence, but in adulthood it is tied more strongly to depression. However, not all inhibited children develop anxiety or depression,” Tang said. “It was particularly the inhibited children who showed blunted striatal activity who were more likely to become more depressed in young adulthood.” Pressure chamber therapy is effective in the functional improvement of autism, study finds Tel-Aviv University (Israel), October 26, 2022 A new Tel Aviv University study succeeded in significantly improving social skills and the condition of the autistic brain through pressure chamber therapy. The study was conducted on animal models of autism. In it, the researchers identified changes in the brain, including a reduction in neuroinflammation, which is known to be associated with autism. Moreover, a significant improvement was found in the social functioning of the animal models treated in the pressure chamber. The study's success has many implications regarding the applicability and understanding of treating autism using pressure chamber therapy. Fischer and Barak explain that hyperbaric medicine is a form of therapy in which patients are treated in special chambers where the atmospheric pressure is higher than the pressure we experience at sea level, and in addition are delivered 100% oxygen to breathe. Dr. Barak says that “the medical causes of autism are numerous and varied, and ultimately create the diverse autistic spectrum with which we are familiar. About 20% of autistic cases today are explained by genetic causes, that is, those involving genetic defects, but not necessarily ones that are inherited from the parents.” “Despite the variety of sources of autism, the entire spectrum of behavioral problems associated with it are still included under the single broad heading of ‘autism,' and the treatments and medications offered do not necessarily correspond directly to the reason why the autism developed.” Dr. Barak says that they “discovered that treatment in the oxygen-enriched pressure chamber reduces inflammation in the brain and leads to an increase in the expression of substances responsible for improving blood and oxygen supply to the brain, and therefore brain function. In addition, we saw a decrease in the number of microglial cells, immune system cells that indicate inflammation, which is associated with autism. “To our surprise, the findings showed a significant improvement in the social behavior of the animal models of autism that underwent treatment in the pressure chamber compared to those in the control group, who were exposed to air at normal pressure, and without oxygen enrichment.” Study reveals connection between microbiome and autoimmune disorders University of Calgary, October 23, 2022 Published in Cell, a study by Santamaria and Kathy McCoy, PhD, from the University of Calgary's Cumming School of Medicine (CSM) reveals a new mechanism in the gut microbiome that regulates pro- and anti-inflammatory cells. “We found that a protein expressed by gut bacteria called Bacteroides works to prevent IBD by rapidly recruiting white blood cells to kill a cell of the immune system that is responsible for orchestrating inflammatory bowel disease (IBD),” says McCoy. “We think that this mechanism is likely involved in preventing most people from developing IBD.” However, there is a flipside to the protein's call for help. “In some people, the white blood cells overreact to the presence of the IBD bacteria. This is what causes problems like IBD—it's not the bacteria itself, but the immune system's severe reaction triggered by the protein. These same overstimulated white blood cells are also the cells that cause other autoimmune disorders like diabetes,” says Santamaria. “This discovery demonstrates the effect the gut microbiome has on the immune system and unearths a novel mechanism via which changes in the gut microbiome can increase the risk of autoimmune disorders. While we looked specifically at IBD, it is likely there are many proteins in the gut that contribute to the development of other autoimmune disorders via similar mechanisms.”

Come join Christian and Mike as they discuss how birth, feeding and environmental factors affect the gut, brain and neurodevelopment through the lens of the microbiome. Pika pika. References for those playing at home: 1. Kerns CM, Winder-Patel B, Iosif AM, et al. Clinically Significant Anxiety in Children with Autism Spectrum Disorder and Varied Intellectual Functioning. J Clin Child Adolesc Psychol. 2021;50(6):780-795. 2. Neurodevelopmental Disorders. Diagnostic and Statistical Manual of Mental Disorders. Published online May 22, 2013. 3. Restrepo B, Angkustsiri K, Taylor SL, et al. Developmental–behavioral profiles in children with autism spectrum disorder and co-occurring gastrointestinal symptoms. Autism Research. 2020;13(10):1778-1789. 4. Wexler HM. Bacteroides: the Good, the Bad, and the Nitty-Gritty. Clinical Microbiology Reviews. 2007;20(4):593. 5. Ho LKH, Tong VJW, Syn N, et al. Gut microbiota changes in children with autism spectrum disorder: A systematic review. Gut Pathogens. 2020;12(1):1-18. 6. Vaiserman A, Romanenko M, Piven L, et al. Differences in the gut Firmicutes to Bacteroidetes ratio across age groups in healthy Ukrainian population. BMC Microbiology. 2020;20(1):1-8. 7. Stojanov S, Berlec A, Štrukelj B. The Influence of Probiotics on the Firmicutes/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel disease. Microorganisms 2020, Vol 8, Page 1715. 2020;8(11):1715. 8. Rizzardi KF, Indiani CM dos SP, Mattos-Graner R de O, de Sousa ET, Nobre-dos-Santos M, Parisotto TM. Firmicutes Levels in the Mouth Reflect the Gut Condition With Respect to Obesity and Early Childhood Caries. Frontiers in Cellular and Infection Microbiology. 2021;11:472. 9. Magne F, Gotteland M, Gauthier L, et al. The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients? Nutrients. 2020;12(5). 10. Korpela K. Impact of Delivery Mode on Infant Gut Microbiota. Ann Nutr Metab. 2021;77:11-19. 11. Niu J, Xu L, Qian Y, et al. Evolution of the Gut Microbiome in Early Childhood: A Cross-Sectional Study of Chinese Children. Frontiers in Microbiology. 2020;11:439. 12. Lin CW, Septyaningtrias DE, Chao HW, et al. A common epigenetic mechanism across different cellular origins underlies systemic immune dysregulation in an idiopathic autism mouse model. Molecular Psychiatry 2022. Published online May 2, 2022:1-12. 13. Liu F, Li J, Wu F, Zheng H, Peng Q, Zhou H. Altered composition and function of intestinal microbiota in autism spectrum disorders: a systematic review. Translational Psychiatry 2019 9:1. 2019;9(1):1-13. 14. de Angelis M, Francavilla R, Piccolo M, de Giacomo A, Gobbetti M. Autism spectrum disorders and intestinal microbiota. https://doi.org/101080/1949097620151035855. 2015;6(3):207-213. 15. Wang M, Li M, Wu S, et al. Fecal Microbiota Composition of Breast-fed Infants is Correlated with Human Milk Oligosaccharides Consumed. J Pediatr Gastroenterol Nutr. 2015;60(6):825. 16. Martin R, Makino H, Yavuz AC, et al. Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota. PLoS One. 2016;11(6). 17. Rutayisire E, Huang K, Liu Y, Tao F. The mode of delivery affects the diversity and colonization pattern of the gut microbiota during the first year of infants' life: A systematic review. BMC Gastroenterology. 2016;16(1).

Could probiotics restore microbiome imbalance linked to autoimmune disorder? UCLA and Oslo University Probiotics might help restore gut bacterial imbalance in patients with systemic sclerosis, says a new study looking at gastrointestinal bacterial compositions in two geographically-distinct populations suffering from the autoimmune disorder. Systemic sclerosis is an autoimmune disease which impacts the body's connective tissue. It is an uncommon condition that results in hard, thickened areas of skin and sometimes problems with internal organs and blood vessels.The study ran across the US and Norway and found that Norwegians and Americans with systemic sclerosis had higher levels of bacteria which can cause inflammation and lower levels of bacteria which are said to protect against inflammation compared to those not suffering from systemic sclerosis.The study found that those with systemic sclerosis had significantly lower levels of gut bacteria which is thought to protect against inflammation, such as Bacteroides.They were also found to have higher amounts of bacteria which promote inflammation, such as Fusobacterium, in comparison to those without systemic sclerosis.The study suggests that probiotics may aid restoring gut bacterial balance in those suffering from systemic sclerosis.   Caraway extract shows slimming potential for women University of Malaya (Malaysia),  An aqueous extract of caraway seeds may suppress appetite and help slim waistlines and thighs in physically active women, says a new study. Data published in Phytotherapy Research indicated that 90 days of supplementation with the caraway (Carum carvi L.) extract led to significant reductions in waist circumference of 6.2 cm and thigh circumference of 5.4 cm, compared to baseline levels. No significant waist reductions were recorded in the placebo group. “This study showed that the consumption of 30 mL/day CAE [caraway aqueous extract] may result in reasonable anti-obesity effects,” wrote the researchers. “Most likely, this occurs through a combination of four major bioactivities, including anti-microbial, anti-oxidant, and anti-inflammatory properties, together with the appetite-suppressing activity. Scientists from the University of Malaya (Malaysia), Shahid Beheshti University of Medical Sciences (Iran), and Natural Products Inc (USA) recruited 70 aerobically trained, overweight, and obese women to participate in their triple-blind, placebo-controlled, clinical study. The women – who were instructed to not change their diet or physical activity – were randomly assigned to receive either the caraway extract or placebo for 90 days. Results showed that women in the caraway group had significant reductions in both appetite levels and carbohydrate intake compared with the placebo group. Commenting on the potential bioactives compounds responsible for the effects, the researchers note that caraway seed extracts contain volatile compounds such as limonene, gamma-terpinene, trans-carveol, carvone, thymol, and carvacrol. Friends Provide Better Pain Relief Than Morphine, Oxford University Study Reveals Oxford University Recent studies have explored the science behind friendships and discovered that there are actually measurable differences between people who have strong, healthy social networks and those who don't. In particular, people with strong friend connections were found to experience significantly better states of physical and mental health. “People with social support have fewer cardiovascular problems and immune problems, and lower levels of cortisol — a stress hormone,” says Tasha R. Howe, PhD, associate professor of psychology at Humboldt State University. Adding to the growing research on the benefits of friendship, a recent study conducted by researchers at Oxford University established that people with more friends have higher pain tolerance.  The study was designed to use pain tolerance to test the brain's endorphin activity. The researchers theorised that people with larger social networks would, as a result, have higher pain tolerance. The findings of the study supported their theory in that it showed that indeed, strong social connections were correlated with higher pain tolerance. As mentioned in the final statement it is not just the size of our social network that is important to our wellbeing, but the quality of the friendships that matters as well. With the advent of the internet modern society is changing quickly, and our interactions are increasingly occurring online. Even though the internet can be a great way to connect with likeminded people, online friends just aren't the same as those we can actually sit with and look directly in the eye when we communicate–and a digital hug is just nowhere near as good as a real one!  Videos: 1. Pfizer CEO Albert Bourla explains Pfizer's new tech to Davos crowd (0:25) 2. You'll Never See This on Tell Lie Vision (2:19) 3. Jimmy Dore-  TV War “Experts” Revealed As Paid Shills For Weapons Manufacturers  (only first 6:00) 5. SHOCKING! Assad Spills Truth About Ukraine Conflict and NATO by Richard Medhurst (11:50)

Broccoli may beneficially affect microbiota diversity: Study University of Illinois Consuming broccoli may change the diversity and composition of the microbiota in the gastrointestinal tract, says a new study. Two hundred grams per day of broccoli for 17 days resulted in 37% increase in the proportion of Bacteroidetes relative to Firmicutes, according to data presented at the Experimental Biology meeting in Chicago this week by scientists from the University of Illinois at Urbana-Champaign, ARS-USDA, and the National Cancer Institute. “These novel results reveal that broccoli consumption affects the diversity and composition of the GI microbiota of healthy adults,” they wrote in the FASEB Journal . “These data help fill the gap in knowledge related to the role of bacterial hydrolysis of phytonutrients. “The increase in Bacteroides spp. is particularly relevant because Bacteroides thetaiotaomicron has been shown in vitro to utilize glucosinolates.”   Acupuncture possible treatment for dental anxiety University of York Researchers have found evidence that acupuncture could help people who experience dental anxiety. Dental anxiety affects up to an estimated 30% of the adult population in countries world-wide. Patients can experience nausea, difficulty breathing and dizziness at the thought of going to the dentist, during an examination, and following treatment. In a review of six trials with 800 patients, researchers used a points scale to measure anxiety and studies show that anxiety reduced by eight points when dental patients were given acupuncture as a treatment. This level of reduction is considered to be clinically relevant, which means that acupuncture could be a possibility for tackling dental anxiety. Studies that compared anxiety levels between patients that received acupuncture and those that did not, showed a significant difference in anxiety scores during dental treatment. A clinically relevant reduction in anxiety was found when acupuncture was compared with not receiving acupuncture.   Omega-3 may help protect against adverse cardiovascular effects of pollution Case Western University An article published in the Journal of the American College of Cardiology reported a protective effect for supplementation with omega-3 fatty acids against some of the harmful cardiovascular effects of exposure to air pollution in China. The randomized, double-blinded trial included 65 healthy college students in Shanghai, China who received 2.5 grams fish oil as a source of omega-3 fatty acids or a placebo daily. During the last two months of the trial, the subjects participated in four health examinations that included blood pressure assessment and measurement of blood markers of inflammation, coagulation, endothelial function, oxidative stress, antioxidant activity, cardiometabolism and neuroendocrine stress response. Campus levels of fine particulate matter air pollution (PM 2.5) measured during the course of the trial averaged 38 micrograms per cubic meter. The researchers observed greater stability of most biomarker levels in responses to changes in fine particulate matter exposure in the fish oil-treated group in comparison with the placebo group. Omega-3 fatty acid supplementation was associated with beneficial effects for five blood biomarkers of inflammation, coagulation, endothelial function, oxidative stress, and neuroendocrine stress response.      Snoring causes injuries and prevention of healing in the upper airways Umea University (Sweden) The recurrent vibrations caused by snoring can lead to injuries in the upper airways of people who snore heavily. This in turn, can cause swallowing dysfunction and render individuals more vulnerable for developing the severe condition obstructive sleep apnea. These findings are reported by researchers at Umeå University, Sweden. Their on-going research focuses on the processes behind vibratory damage and healing of the upper airway tract. The data generated will help identify people at high risk of developing sleep apnea and to find novel treatment strategies. Researchers in Umeå have shown that snorers and sleep apnea patients have neuromuscular injuries in the upper respiratory tract. The injuries can be seen at both the structural and molecular level. Researchers could also observe a correlation between snoring and swallowing dysfunction as well as a relation between nerve damage and obstructive sleep apnea. Sleep apnea is characterized by repeated collapse of the upper respiratory tract leading to respiratory arrest during sleep, which increases the risk of cardiovascular disease. The studies show that people who constantly snore heavily and have sleep apnea displayed a loss of nerves and muscle mass in the soft palate. Furthermore, the attempts by the body to heal damaged tissue were disturbed resulting in an abnormal muscle structure. Another interesting finding was that muscle fibres in the soft palate lacked or had a disturbed organization of certain structural proteins. These proteins stabilize the organelles of the muscle cell and support cellular structures related to energy production and muscle fibre contraction. The researchers also found that a neurotransmitter that is normally associated with healing and regeneration of neurons was present in the muscle cells. This finding suggests that the body is trying to heal the injuries, but the recurrent snoring vibrations prevent proper healing. It becomes a vicious circle where snoring causes damage and at the same time disturb healing of injuries, which can lead to swallowing dysfunction and sleep apnea.   Study: Tai chi can reduce hypertension symptoms in young and middle-aged in-service staff Zhei-jian Hospital (China) Researchers from Zhejiang Hospital in China reported that practicing t'ai chi can help with hypertension.  The treatment group practiced simplified t'ai chi for three months. On the other hand, the control group underwent general daily lifestyle intervention. After one month of exercise, the participants who practiced t'ai chi experienced significant reductions in their systolic blood pressure, heart rate, triglycerides, total cholesterol, and low-density lipoprotein (LDL) cholesterol. At the end of the intervention period, the t'ai chi group experienced substantial decreases in their BMI, heart rate, systolic blood pressure, diastolic blood pressure, pulse pressure, triglycerides, total cholesterol, LDL cholesterol, and blood sugar levels. Practicing t'ai chi also improved their quality of life.   Lemongrass essential oil protects the liver from acetaminophen-induced injury State University of Maringa (Brazil) A study published in The American Journal of Chinese Medicine found that the essential oil extracted from lemongrass (Cymbopogon citratus) can protect the liver from damage caused by acetaminophen intake.  They pretreated mice with 125, 250, or 500 milligrams per kilogram (mg/kg) of lemongrass essential oil or 200 mg/kg of a standard drug per day for seven days. Then, they induced liver toxicity by administering 250 mg/kg dose of acetaminophen. The researchers found that pretreatment with lemongrass essential oil significantly reduced the levels of liver disease markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP). Inflammation in the liver was also reduced by lemongrass essential oil. Liver lesions in mice were also improved after pretreatment with lemongrass essential oil. Pretreatment with lemongrass essential oil increased antioxidant activity in the liver. Videos:  2022.05.05 Zelensky Is Trapped (8:07)  

Today, I am blessed to have here with me Dr. Shayne Morris. He has unique and broad experiences, for over 30 years, in the nutritional industry and scientific community. Trained first in the ways of natural product sourcing, quality, design and manufacturing which, quickly led to the pursuit of a formal education in chemistry, microbiology, and finally a Ph.D. in molecular biology and biochemistry. Passionate about owning a business in the industry, Dr. Shayne Morris also earned a Master's in Business degree. He is an adjunct professor in chemistry at WSU and is a Certified Nutrition Specialist in the American College of Nutrition. Dr. Shayne Morris has authored a number of peer-reviewed journal articles, scientific abstracts, talks and patents in the areas of biological chemistry, natural products and product development. Recent significant research is focused on our microbiome and the probiotic potential of unique human microbes. As part of Dr. Shayne Morris' research his lab has developed unique growing and stabilizing methods for important commensal organisms like Bacteroides, Akkermansia, beneficial phage and more. Not only are personalized microbes important the nature of their food and metabolites are equally important to the microbiome as a whole and the human symbiosis. Therefore, prebiotic research has become an inseparable component of the probiotic research and in some cases more impactful than probiotics alone. In this episode, Dr. Shayne Morris opens the show by discussing how he became invested in the microbiome. Ketosis is fantastic for the microbiome; Dr. Morris explains what benefits are taking place in the gut when you're burning ketones. We have 10 trillion cells in the human body, and each has its own job; Dr. Morris reveals how you can help your cells complete their job as efficiently as possible. Tune in as we chat about your microbiome's circadian rhythm, the importance of bile, and Systemic Formulas. 90 Day Detox Program: http://www.ketokampdetox.com Order Keto Flex: http://www.ketoflexbook.com -------------------------------------------------------- / / E P I S O D E   S P ON S O R S  PureForm Omega Plant Based Oils (Best Alternative to Fish Oil): http://www.purelifescience.com Use ben4 for $4.00 off. Paleo Valley beef sticks, apple cider vinegar complex, organ meat complex & more. Use the coupon code KETOKAMP15 over at https://paleovalley.com/ to receive 15% off your entire order. Upgraded Formulas Hair Mineral Deficiency Analysis & Supplements: http://www.upgradedformulas.com Use KETOKAMP15 at checkout for 15% off your order.  Text me the words "Podcast" +1 (786) 364-5002 to be added to my contacts list.  [01:10] How Dr. Shayne Morris Got Involved In The Health Space When Dr. Morris got into the health space, there was very little hard science on the miraculous nature of how herbs work. To learn more, Dr. Morris buried himself into the educational side and went after microbiological degrees along with biochemical degrees. It wasn't until the 2000s that we identified the importance of microbes. Remember, we're a human built from about 10 trillion cells. Now, Dr. Morris has a research lab on the microbiome and develops products to improve the microbiome. [08:50] Why Dr. Shayne Morris Is Such A Big Fan of Keto One of the most brilliant aspects of adapting to keto is for people that are struggling with metabolic issues. Every organ in the body can utilize ketones. Ketones can really change the way that mitochondria work. Plus, ketones can affect the oxidative stress that cells are under. On a cellular level, ketones offer so much benefit in terms of their energy production. Lastly, we're genetically predesigned to store fats. [17:20] We Have 10 Trillion Cells, and Each Cell Has Its Own Job We are a complex of 10 trillion cells. Each cell has its own job. For instance, the cells in the eye behave very differently than the cells in the brain. Each and every one of those cells has a very specific set of duties. For a cell to do its job, it needs energy! Overall, we want to generate more positive genetic outcomes on the cellular level. [24:40] How Your Gut Affects Your Whole Body There's a complexity of color that we see in nature. When you eat different compounds, you are feeding the microbiome. We have to think about the microbiome as the gateway to all the things we need in our bodies. Our gut, anatomically, is the largest immune system. Plus, it is the largest innervated system outside of the brain. The gut controls everything. Your microbiome is what's directing all of the traffic in the body. [30:15] Why Burning Sugar Is Producing More Cellular Inflammation When you look at burning sugar, there's a time and a place. Burning sugar is a quick way to release energy. When you eat sugar, it should come from plants. Sugar and flour are not good sources of carbs. Burning sugar can generate free radicals. When you're flooding the mitochondria with just sugar, it gets overwhelmed. All these signals are going out into the cell, saying we're broken, and it's time to shut down. [40:25] Do You Really Need To Eat Vegetables? Your microbiome has a circadian rhythm. That rhythm isn't just based on the moon or the sun; it's based on the nutrients we get. If we're in winter, we have a different microbial rhythm than we do in the summer. These rhythms are part of the more, the greater picture of diet. Throughout the winter, there typically weren't fruits and vegetables to eat. Instead, people would eat fats and meats. Our microbiome is supremely adapted to function on these rhythms and on these different diets. When you rotate your diet, it creates diversity. [59:00] Learn More About Systemic Formulas: Lb – Liver/Gall Bladder Check out Lb here: https://revelationhealth.com/products/systemic-formulas-61-lb-liver-gall-bladder?_pos=2&_sid=a6614201f&_ss=r/azadi?afmc=azadi This formula was designed to help the body maintain proper portal duct function. It assists in purifying the blood of mucus-forming matter. There are a number of herbs that we know can drive up bile production. Plus, all these mechanisms or pathways that help us produce those so you can generate enough bile. If you take enzymes, they help break down the lipids, the carbohydrates, and the proteins. Probiotics and prebiotics will drive up the quality and quantity of bile needed to address healthy fats. AND MUCH MORE! Resources from this episode: Check out Dr. Shayne's Website: https://drshaynemorris.com/ My Byome: https://mybyome.com/ Learn more about Systemic Formulas: https://systemicformulas.com/ Follow Dr. Shayne Morris Instagram: https://www.instagram.com/drshaynemorris/ Facebook: https://www.facebook.com/drshaynemorris/ YouTube: https://www.youtube.com/channel/UCTOm0SSKJulize06GMzEM-A Check out Terra: https://revelationhealth.com/products/mybiome-terra-byome-60-caps/azadi?afmc=azadi   Get Lb here: https://revelationhealth.com/products/systemic-formulas-61-lb-liver-gall-bladder?_pos=2&_sid=a6614201f&_ss=r/azadi?afmc=azadi Learn more about Immuno Pre-Byome: https://revelationhealth.com/products/mybiome-367-neuro-prebyome-300g/azadi?afmc=azadi Keto Kamp Supplements: http://ketokampsupplements.com/ Join theKeto Kamp Academy: https://ketokampacademy.com/7-day-trial-a WatchKeto Kamp on YouTube: https://www.youtube.com/channel/UCUh_MOM621MvpW_HLtfkLyQ 90 Day Detox Program: http://www.ketokampdetox.com Order Keto Flex: http://www.ketoflexbook.com -------------------------------------------------------- / / E P I S O D E   S P ON S O R S  PureForm Omega Plant Based Oils (Best Alternative to Fish Oil): http://www.purelifescience.com Use ben4 for $4.00 off. Paleo Valley beef sticks, apple cider vinegar complex, organ meat complex & more. Use the coupon code KETOKAMP15 over at https://paleovalley.com/ to receive 15% off your entire order. Upgraded Formulas Hair Mineral Deficiency Analysis & Supplements: http://www.upgradedformulas.com Use KETOKAMP15 at checkout for 15% off your order.  Text me the words "Podcast" +1 (786) 364-5002 to be added to my contacts list.  *Some Links Are Affiliates* // F O L L O W ▸ instagram | @thebenazadi | http://bit.ly/2B1NXKW ▸ facebook | /thebenazadi | http://bit.ly/2BVvvW6 ▸ twitter | @thebenazadi http://bit.ly/2USE0so ▸clubhouse | @thebenazadi Disclaimer: This podcast is for information purposes only. Statements and views expressed on this podcast are not medical advice. This podcast including Ben Azadi disclaim responsibility from any possible adverse effects from the use of information contained herein. Opinions of guests are their own, and this podcast does not accept responsibility of statements made by guests. This podcast does not make any representations or warranties about guests qualifications or credibility. Individuals on this podcast may have a direct or non-direct interest in products or services referred to herein. If you think you have a medical problem, consult a licensed physician.  

Here are the things to expect in this episode:What is the involvement of carbohydrates in digestive health?How do you identify if you have gastrointestinal issues? What tests should you take?How do you get a better balance in your gut health?The five carbs that should be eliminated for people who have gut issues.What is the fast tract diet?And much more!About Dr. Norm Robillard:Norm Robillard, Ph.D. (Norman John Robillard), Founder of Digestive Health Institute, is a gut health expert, author, and microbiologist. He is the creator of the Fast Tract Diet – Fermentation Potential (FP) system, author of the Fast Tract Digestion book series, and publisher of the Fast Tract Diet mobile app.Dr. Norm received his Ph.D. in microbiology from the University of Massachusetts, Amherst studying Bacillus anthracis and other Bacillus species. His post-doctoral training at Tufts University, Boston, focused on antibiotic resistance gene transfer. He was the first to demonstrate the transfer of genes (via conjugation) between the anaerobic gut microbes Bacteroides fragilis and E. coli.During his career in pharma/biotech, Dr. Norm studied the mechanisms of antibiotic action and the genetics of antibiotic resistance. His work contributed to the development and approval of ciprofloxacin, a life-saving antibiotic. However, he always recommended a cautious approach with antibiotics balancing the benefits with the risks and side effects.Beyond antibiotics, Dr. Norm worked on various other projects, including septic shock, viral illnesses and other antibiotics, antiviral and antibody-based therapies.Connect with Dr. Norm!Website: https://digestivehealthinstitute.org/ *includes link to mobile app*Facebook:  https://www.facebook.com/groups/FastTractDiet/Books”Fast Tract Digestion: Heartburn - https://www.amazon.com/Heartburn-Digestion-Surprising-Explained-Clinically-ebook/dp/B007WZHCWKFast Tract Digestion: IBS - https://www.amazon.com/IBS-Irritable-Bowel-Syndrome-Antibiotics-ebook/dp/B00CBP2S1QConnect with Denise DeShetler!Website: https://www.passionatehealthadvocate.com/Facebook: https://www.facebook.com/groups/phapodcastjunkiesLinkedIn: https://www.linkedin.com/in/denisedeshetlerInstagram:  https://www.instagram.com/passionatehealthadvocate/

Wet weather this spring and summer has certainly created ideal conditions for foot problems in sheep. Nearly continuous exposure to moisture softens the hoof's horny tissues and makes it more vulnerable to irritation, injury, and infection. Those flocks that are affected by classic virulent foot rot (sometimes called contagious foot rot) have likely seen a surge in the number and severity of cases if they have not been attempting to control or eradicate this potentially devastating disease.Those flock owners who have experienced milder forms of lameness in their flocks may assume that they don't have foot rot but have a milder condition called “foot scald” or “scald.” Actually there are really two recognized conditions that are sometimes referred to as “scald.” At first the difference may seem academic, but for some producers, it may be more than that.Virulent, or contagious, foot rot is caused by a synergistic infection with two organisms, Dichelobacter nodosus (formerly Bacteroides nodosus) and Fusobacterium necrophorum. This last organism is in virtually all sheep environments and sets the stage for infection with the organism necessary for foot rot to occur — Dichelobacter nodosus. This organism produces a powerful proteolytic enzyme that dissolves hoof horn and leads to the undermining of the sole, the severe lameness, the foul smell, and the abnormal hoof growth seen with classic virulent foot rot. About 20 different strains of D. nodosus are believed to occur in the US.True foot rot does not occur in the absence of D. nodosus. However, a less persistent and generally milder condition in which only inflammation between the toes and a slight under-running of the hoof horn occurs in some flocks. Both D. nodosus and F. necrophorum can be isolated from these cases, but the strains of D. nodosus isolated seem have a reduced virulence or ability to produce disease. This condition is technically referred to as benign foot rot but has also been called foot “scald.” It is believed that the strains of D. nodosus that are involved are weak enzyme producers and are less able to produce the severe damage seen with virulent foot rot.Another infectious and inflammatory condition which involves only the skin between the claws without significant undermining of the horny tissue has been termed ovine interdigital dermatitis (OID), and it has also been called “scald.” The bacteria associated with this condition are F. necrophorum and Actinomyces pyogenes; both of which tend to be common in typical sheep environments. D. nodosus is not involved. The disease usually only occurs when the weather and other conditions on the farm damage the skin and allow these bacteria to create skin infections.  Because the term “scald” has been applied to both OID and benign foot rot, the use of that term can be misleading.  Both conditions usually cause only mild or temporary lameness that may be obvious only in wet periods of the year. From a practical standpoint, the two conditions are difficult to distinguish from one another, and laboratory capability to isolate and serotype D. nodusus is generally not readily available. Foot baths and soaks with 10% zinc sulfate usually result in improved healing of either condition. Foot “scald” often disappears when the environmental conditions become dry.So if the two conditions called “scald” are not easy to differentiate and they both tend to clear up with foot bathing or dry weather, why even bother to make the distinction? There are two reasons that may be important to some producers. The first is that all the strains of D. nodosus, whether they produce virulent or benign foot rot, are maintained in the flock by sheep that harbor the infection in cracks and crevices on their feet — carrier animals. That means that most likely, unless an attempt at eradication is made, benign foot rot will be back again as soon as the weather conditions favorable for foot softening&

047:  EASIEST Way to INTERMITTENT Fast; CIRCADIAN Fasting, What it is and How You CAN Do it Simply and the the Myriad of Benefits.In this episode, Dr. Thomas Hemingway gives an update on Intermittent Fasting, and specifically addresses Circadian Fasting which may be the EASIEST way to Fast and is NATURAL and Simple.He also shares a couple interesting articles from the New England Journal of Medicine and JAMA (Journal of American Medical Association) which share the Multiple Benefits of Intermittent Fasting and How EASY and BENEFICIAL it can be.  HAVE A LISTEN AND TRY IT OUT!Learn more about Thomas Hemingway, MD and upcoming episodes, tips, tricks and more here: www.modernmedicinemovement.com on Instagram at @modermedicinemovement or @alohasurfdocAsk to join his FREE Private Facebook health Group with weekly LIVE educational sessions entitled:Modern Medicine Movement Health and Wellness Grouphttps://www.facebook.com/groups/2543880582493990/?ref=shareAlthough Dr. Thomas Hemingway is a physician, he is NOT your physician and is NOT to replace your primary care physician/health care provider. This podcast is NOT to be construed as medical advice by Dr. Thomas Hemingway or the guests comments as they are opinion only and NOT medical advice. Please consult your physician/health care provider should you have any medical questions or before trying any new practice. Check out these references he referred to in the podcast:1.    NEJM Dec 26, 2019 “Effects of Intermittent Fasting on Health, Aging, and Disease, Rafael de Cabo, Ph.D., and Mark P. Mattson, Ph.D.https://www.nejm.org/doi/full/10.1056/nejmra19051362.  Turk J Gastroenterology 2019 Dec;30(12):1030-1035. doi: 10.5152/tjg.2019.19185.Islamic fasting leads to an increased abundance of Akkermansia muciniphila and Bacteroides fragilis group: A preliminary study on intermittent fastingCeren Özkul 1, Meltem Yalınay 2, Tarkan Karakan 3https://pubmed.ncbi.nlm.nih.gov/31854308/3.  Prolonged Nightly Fasting and Breast Cancer Prognosis, JAMA oncology.Catherine R. Marinac, BA, Sandahl H. Nelson, MS, Caitlin I. Breen, BS, BA, Sheri J. Hartman, PhD, Loki Natarajan, PhD, John P. Pierce, PhD, Shirley W. Flatt, MS, Doroth

Let's get on to Macrolides, Lincosamides. A little bit of stuff on protein biosynthesis won't hurt to help us understand the pharmacology of these class of drugs, macrolides and Lincosamides. Bacterial protein synthesis involves proteins required for reproduction, and is made possible by ribosomal RNA, mRNA and tRNA. To begin, the double stranded DNA first unwinds in an untwisting motion in the region which codes for the specific protein to be made and only that one strand of the DNA serves as a template for what is known as transcription. RNA polymerase makes a copy of this segment, which now stands as what is called mRNA. Once the strand of mRNA is complete, it detaches from that segment, and in turn become attached to ribosomes. Now it gets interesting. Bacterial ribosomes are made of two subunits, the small 30s and a bigger 50s ribosomal subunits, together makes up 70s ribosomal unit. The numbers don't add up right? Yes 30+50 is not 70. If you want to know why, download the Podroom app and join the discussion, there you can ask me and I'll explain. For now, we move. The ribosomal subunits attach to the mRNA strand like a zipper and begin the synthesis of the polypeptide chain, along that strand. Now the amino acids needed for this synthesis, is bound to tRNA, so tRNA + amino acids bind to the ribosome which is on the mRNA strand and begins to work its way from one end of the strand to the other, making the polypeptide chain in the process, until it hits a stop codon which makes it stop and release the full polypeptide chain it has been making. The 70s ribosome couples itself back and awaits further instruction. It's very easy, see, these are the steps 1.    Bacterial DNA unwinds to reveal a segment to be copied 2.    RNA polymerase makes a copy of this segment, a complete mirror image of the segment, detaches this new copy, which now stands alone as mRNA 3.    This mRNA attaches to 70s ribosome, which clasps the strands above and below with its two subunits 50s and 30s 4.    tRNA which contains amino acids is then bound to the ribosome and this moves along the mRNA strand to synthesize the polypeptide chain. 5.    Macrolides and Lincosamides inhibit this ribosome and do not allow it to move. If it cannot move, polypeptide and hence protein synthesis stops, and bacteria cannot grow, everything becomes static, that is why they say these drugs are bacteriostatic. So now, drugs that affect ribosomes in protein synthesis either affect the 50s or 30s subunits of the 70s ribosome. Don't worry, there is a mnemonic for that. Buy AT 30 and CELL @50 Aminoglycosides and tetracyclines inhibit protein synthesis by inhibiting the 30s ribosomal subunit. Chloramphenicol, Erythromycin (macrolides), Lincosamides and Linezolid all inhibit 50s ribosomal subunit. So macrolides – are a class of antibiotics that contain the following drugs 1.    Erythromycin – the oldest, strep, staph, pertusis, diphtheria, M. pnemonia 2.    Clarithromycin- strongly g +ve, used in eradication of H. pylori, renal toxicity 3.    Azithromycin – strong G -ve, RTI mainly As you go from erythromycin to azithromycin, you go from old to new, and also their half lives increases in that fashion, and hence their frequency of dosing reduces. *MOA* - just like I said, inhibits 50s, along with other counterparts in the mnemonic CELL @50 *Spectrum of activity* – G -ve and +ve, anaerobes (upper airway), atypical bacteria (legionella, chlamydia, mycoplasma etc), others like mycobacterium avium complex, campylobacter, treponema pallidum etc *Absorption* - food decreases it, why enteric coated ones are made. Clarithromycin is well absorbed irrespective of food. *Distribution-* all body fluids and placenta except CSF *and Elimination* - Hepatic: ALL, only clarithromycin is partially excreted by renals, why it needs renal adjustment at times. Cannot dialyze. Erythro t1/2- 1.5hrs, clarithromycin about 6hrs, Azithro – 68hrs *Resistance* - 80% is through the active efflux mechanism in which the mef gene encodes for an efflux pump that actively pumps macrolide out of the cell, away from the ribosome it is supposed to inhibit. Another mechanism is one in which a gene alters the binding site of the macrolide on the ribosome. Lastly, there is cross resistance which occurs between all macrolides. *Adverse Reactions* - M- Motility A: Arrythmias (prolonged qt interval) C: Cholestatic Hepatitis R: Rash 0: eosinophilia *Drug interaction* : it inhibits CYP3A4 enzyme leading to increased effects of carbamazepine, theophylline, warfarin, valproate. Enough of Macrolides. Let's talk about a close relative in mechanism of action. The Lincosamides Briefly! In this class is Clindamycin and Lincomycin They are active against staph, gram +ve and -ve anaerobes. Also against Bacteroides. Mechanism of action – You know this already, yes say it, of course if you Cell@ 50 you will know it binds to 50s ribosome and hence inhibits protein synthesis. It is absorbed well, penetrates well into most tissues including bone, but not CSF Excreted via the liver, bile and Urine. Resistance: mechanisms via drug inactivation, alteration of 50s ribosomal subunit by adenine methylation and mutation of the 50s ribosomal protein. *USES:* 1.    Anaerobic infections 2.    Osteomyelitis, arthritis 3.    AIDS related toxoplasmosis (combined with pyrimethamine) 4.    AIDS related pneumocystis carinii pneumonia. ADVERSE REACTIONS: 1.    Severe diarrhea- pseudomembranous enterocolitis caused by clostridium deficille 2.    High IV dose – neuromuscular blockade 3.    Neutropenia 4.    Impaired liver function 5.    Hypersensitivity And that's all fellas. Next, we talk about Sulphonamides in the next episode. This content is made for medical students, all pharmacology enthusiasts and medical practitioners who want to refresh their memory within the shortest possible time. This is meant to be used in conjunction with detailed pharmacology notes or texts, not sufficient as a standalone.

Gary takes on the real issues that the mainstream media is afraid to tackle. Tune in to find out the latest about health news, healing, politics, and the economy.  Gut microbiome implicated in healthy aging and longevity Data from over 9,000 people reveal a distinct gut microbiome signature that is associated with healthy aging and survival in the latest decades of life Institute for Systems Biology (Seattle), February 18, 2021 The gut microbiome is an integral component of the body, but its importance in the human aging process is unclear. ISB researchers and their collaborators have identified distinct signatures in the gut microbiome that are associated with either healthy or unhealthy aging trajectories, which in turn predict survival in a population of older individuals. The work is set to be published in the journal Nature Metabolism. The research team analyzed gut microbiome, phenotypic and clinical data from over 9,000 people - between the ages of 18 and 101 years old - across three independent cohorts. The team focused, in particular, on longitudinal data from a cohort of over 900 community-dwelling older individuals (78-98 years old), allowing them to track health and survival outcomes.  The data showed that gut microbiomes became increasingly unique (i.e. increasingly divergent from others) as individuals aged, starting in mid-to-late adulthood, which corresponded with a steady decline in the abundance of core bacterial genera (e.g. Bacteroides) that tend to be shared across humans. Strikingly, while microbiomes became increasingly unique to each individual in healthy aging, the metabolic functions the microbiomes were carrying out shared common traits. This gut uniqueness signature was highly correlated with several microbially-derived metabolites in blood plasma, including one - tryptophan-derived indole - that has previously been shown to extend lifespan in mice. Blood levels of another metabolite - phenylacetylglutamine - showed the strongest association with uniqueness, and prior work has shown that this metabolite is indeed highly elevated in the blood of centenarians. "This uniqueness signature can predict patient survival in the latest decades of life," said ISB Research Scientist Dr. Tomasz Wilmanski, who led the study. Healthy individuals around 80 years of age showed continued microbial drift toward a unique compositional state, but this drift was absent in less healthy individuals.  "Interestingly, this uniqueness pattern appears to start in mid-life - 40-50 years old - and is associated with a clear blood metabolomic signature, suggesting that these microbiome changes may not simply be diagnostic of healthy aging, but that they may also contribute directly to health as we age," Wilmanski said. For example, indoles are known to reduce inflammation in the gut, and chronic inflammation is thought to be a major driver in the progression of aging-related morbidities. "Prior results in microbiome-aging research appear inconsistent, with some reports showing a decline in core gut genera in centenarian populations, while others show relative stability of the microbiome up until the onset of aging-related declines in health," said microbiome specialist Dr. Sean Gibbons, co-corresponding author of the paper. "Our work, which is the first to incorporate a detailed analysis of health and survival, may resolve these inconsistencies. Specifically, we show two distinct aging trajectories: 1) a decline in core microbes and an accompanying rise in uniqueness in healthier individuals, consistent with prior results in community-dwelling centenarians, and 2) the maintenance of core microbes in less healthy individuals." This analysis highlights the fact that the adult gut microbiome continues to develop with advanced age in healthy individuals, but not in unhealthy ones, and that microbiome compositions associated with health in early-to-mid adulthood may not be compatible with health in late adulthood. "This is exciting work that we think will have major clinical implications for monitoring and modifying gut microbiome health throughout a person's life," said ISB Professor Dr. Nathan Price, co-corresponding author of the paper.      Rosmarinic acid suppresses cognitive decline in Alzheimer disease mouse model University of Tokyo (Japan), February 15, 2021   According to news originating from the University of Tokyo , research stated, “Rosmarinic acid (RA), a polyphenol found in Lamiaceae herbs, is a candidate of preventive ingredients against Alzheimer’s disease (AD) as it potently suppresses the aggregation of amyloid b (Ab); however, the effect of RA on tau phosphorylation and cognitive dysfunction remains unclear.” Financial supporters for this research include Japan Society for the Promotion of Science; Japan Agency for Medical Research and Development; Cross-Ministerial Strategic Innovation Promotion Program. The news editors obtained a quote from the research from University of Tokyo: “The present study revealed that RA intake inhibited the pathological hallmarks of AD, including Ab and phosphorylated tau accumulation, and improved cognitive function in the 3 x Tg-AD mouse model. Additionally, RA intake suppressed hippocampal inflammation and led to the downregulation of the JNK signaling pathway that induces tau phosphorylation. Feeding with RA exerted an anti-inflammatory effect not only in the central nervous system but also in the periphery.” According to the news editors, the research concluded: “Downregulation of the JNK signaling pathway in hippocampus may be a potential mechanism underlying the inhibition of progression of pathology and cognitive deficit by RA feeding.”       Excess fatty tissue accumulated in the neck increases the chances of suffering heart problems, according to a new study University of Granada (Spain), February 15, 2021 Researchers from the University of Granada warn that an accumulation of fatty tissue in the neck (both the double chin and the deeper deposits, located between muscles and around the cervical vertebrae) is a predictor of central and overall adiposity, cardiometabolic risk, and a pro-inflammatory profile in sedentary young adults. Traditionally, the accumulation of visceral adipose tissue has been considered one of the factors most strongly related to cardiometabolic risk and chronic (low-grade) inflammation in humans. However, this well-established association has led researchers to neglect, to some degree, the study of other fatty deposits and their clinical/biological relevance. "Curiously, several studies have demonstrated that the accumulation of fat in the neck (both superficial deposits such as the double chin or jowls and the deeper deposits, located between the muscles and around the cervical vertebrae) increases in direct proportion to the weight or adiposity of the individual and that it follows specific accumulation patterns, according to gender," explains María José Arias Téllez, a researcher at the UGR and one of the main authors of this work.  In fact, a greater accumulation of fat in certain neck tissue compartments, particularly the deeper ones, is linked to a greater likelihood of cardiometabolic risk. Arias Téllez says, "However, the evidence accumulated to date has been based on experiments performed on patients with benign/malignant tumors or other chronic conditions, and it remains to be seen whether it can be generalized to relatively healthy adults." The study carried out at the UGR is part of the ACTIBATE project (Activating Brown Adipose Tissue through Exercise—seeprofith.ugr.es/actibate). The research was led by Jonatan Ruiz Ruiz and its results have been published in the International Journal of Obesity. The study shows that the accumulation of fat in the neck—measured with computed tomography scanning—as well as its distribution in different compartments, is associated with greater overall and central adiposity, greater cardiometabolic risk, and a greater inflammatory status among healthy young adults, regardless of the amount of total and visceral fat. In addition, among the most relevant findings, the researchers observed that this accumulation of fat in the neck was as powerful a factor (in terms of direction and magnitude) as the accumulation of visceral fat in the prediction of cardiometabolic risk and inflammatory status, especially in men. "Therefore, these results underline the need for further research in this new direction, to better understand the effect of fat accumulation in the upper part of the trunk (including the neck) and its clinical repercussions, especially in cardiometabolic riskand inflammation," explains Francisco Miguel Acosta Manzano, one of the main authors of the research. "We still have much work to do. We need to investigate the adipose tissue of the neck in greater depth, to understand its pathogenic role in obesity and associated comorbidities, as well as its biological importance. Furthermore, we only have scant knowledge about the morphological or molecular characteristics of the adipocytes in these deposits, and here basic studies are required. As we increase our knowledge of this deposit, we can also determine whether specific interventions (for example, physical exercise and/or restricted calorie intake) could help reduce the accumulation of fat in the neck (as well as total fat) and implement them clinically," explain Arias Téllez and Francisco Miguel Acosta Manzano, both Ph.D.s students on the Biomedicine program of the UGR's International School for Postgraduate Studies    Effects of saffron extract supplementation on mood, well-being and response to a psychosocial stressor in healthy adults Northumbria University (UK), February 16, 2021 According to news reporting originating from Newcastle upon Tyne, United Kingdom, research stated, “Anxiety, stress, and low mood are closely related and may contribute to depressive symptoms. Among non-pharmacological solutions to improve subclinical mood symptoms and resilience to stress, natural products such as saffron-identified as promising following preliminary beneficial effects in major depressive disorder-represent a relevant strategy.” Our news reporters obtained a quote from the research from Northumbria University: “This study aimed to assess the efficacy of 8 weeks’ supplementation with 30 mg standardized saffron extract on emotional well-being in healthy adults with subclinical feelings of low mood and anxiety and/or stress and evaluate the acute effect of saffron in response to a lab-based psychosocial stressor. The study adopted a double-blind, randomized, parallel groups design in which 56 healthy male and female individuals (18-54 years) received either a saffron extract or a placebo for 8 weeks. Chronic effects of saffron on subjective anxiety, stress, and depressive feelings were assessed using a questionnaire battery [including Profile of Mood State-2, (POMS)] and acute effects in response to a lab-based psychosocial stressor were measured through psychological and physiological parameters. Urinary crocetin levels were quantified. Participants who received the saffron extract reported reduced depression scores and improved social relationships at the end of the study. Urinary crocetin levels increased significantly with saffron supplementation and were correlated with change in depression scores. The typical stress-induced decrease in heart rate variability (HRV) during exposure to the stressor was attenuated following acute saffron intake.” According to the news editors, the research concluded: “Saffron extract appears to improve subclinical depressive symptoms in healthy individuals and may contribute to increased resilience against the development of stress-related psychiatric disorders. Clinical trials number: NCT03639831.”     The science of siestas: New research reveals the genetic basis for daytime napping Massachusetts General Hospital and University of Murcia (Spain), February 13, 2021   How often a person takes daytime naps, if at all, is partly regulated by their genes, according to new research led by investigators at Massachusetts General Hospital (MGH) and published in Nature Communications. In this study, the largest of its kind ever conducted, the MGH team collaborated with colleagues at the University of Murcia in Spain and several other institutions to identify dozens of gene regions that govern the tendency to take naps during the day. They also uncovered preliminary evidence linking napping habits to cardiometabolic health Napping is somewhat controversial,” says Hassan Saeed Dashti, Ph.D., RD, of the MGH Center for Genomic Medicine, co-lead author of the report with Iyas Daghlas, a medical student at Harvard Medical School (HMS). Dashti notes that some countries where daytime naps have long been part of the culture (such as Spain) now discourage the habit. Meanwhile, some companies in the United States now promote napping as a way to boost productivity. “It was important to try to disentangle the biological pathways that contribute to why we nap,” says Dashti.    Previously, co-senior author Richa Saxena, Ph.D., principal investigator at the Saxena Lab at MGH, and her colleagues used massive databases of genetic and lifestyle information to study other aspects of sleep. Notably, the team has identified genes associated with sleep duration, insomnia, and the tendency to be an early riser or “night owl.” To gain a better understanding of the genetics of napping, Saxena’s team and co-senior author Marta Garaulet, Ph.D., of the Department of Physiology at the University of Murcia, performed a genome-wide association study (GWAS), which involves rapid scanning of complete sets of DNA, or genomes, of a large number of people. The goal of a GWAS is to identify genetic variations that are associated with a specific disease or, in this case, habit.   For this study, the MGH researchers and their colleagues used data from the UK Biobank, which includes genetic information from 452,633 people. All participants were asked whether they nap during the day “never/rarely,” “sometimes” or “usually.” The GWAS identified 123 regions in the human genome that are associated with daytime napping. A subset of participants wore activity monitors called accelerometers, which provide data about daytime sedentary behavior, which can be an indicator of napping. This objective data indicated that the self-reports about napping were accurate. “That gave an extra layer of confidence that what we found is real and not an artifact,” says Dashti.   Several other features of the study bolster its results. For example, the researchers independently replicated their findings in an analysis of the genomes of 541,333 people collected by 23andMe, the consumer genetic-testing company. Also, a significant number of the genes near or at regions identified by the GWAS are already known to play a role in sleep. One example is KSR2, a gene that the MGH team and collaborators had previously found plays a role in sleep regulation.   Digging deeper into the data, the team identified at least three potential mechanisms that promote napping: Sleep propensity: Some people need more shut-eye than others. Disrupted sleep: A daytime nap can help make up for poor quality slumber the night before. Early morning awakening: People who rise early may “catch up” on sleep with a nap.   “This tells us that daytime napping is biologically driven and not just an environmental or behavioral choice,” says Dashti. Some of these subtypes were linked to cardiometabolic health concerns, such as large waist circumference and elevated blood pressure, though more research on those associations is needed. “Future work may help to develop personalized recommendations for siesta,” says Garaulet.  Furthermore, several gene variants linked to napping were already associated with signaling by a neuropeptide called orexin, which plays a role in wakefulness. “This pathway is known to be involved in rare sleep disorders like narcolepsy, but our findings show that smaller perturbations in the pathway can explain why some people nap more than others,” says Daghlas.   One or more soda a day could decrease chances of getting pregnant Boston University School of Public Health,  February 13, 2021 The amount of added sugar in the American diet has increased dramatically over the last 50 years. Much of that increase comes from higher intake of sugar-sweetened beverages, which constitute approximately one-third of the total added sugar consumption in the American diet. While consumption of these beverages has been linked to weight gain, type 2diabetes, early menstruation, and poor semen quality, few studies have directly investigated the relationship between sugary drinks and fertility. Now, a new study led by Boston University School of Public Health (BUSPH) researchers has found that the intake of one or more sugar-sweetened beverages per day—by either partner—is associated with a decreased chance of getting pregnant. The study was published in Epidemiology. "We found positive associations between intake of sugar-sweetened beverages and lower fertility, which were consistent after controlling for many other factors, including obesity, caffeine intake, alcohol, smoking, and overall diet quality," says lead author Elizabeth Hatch, professor of epidemiology. "Couples planning a pregnancy might consider limiting their consumption of these beverages, especially because they are also related to other adverse health effects." About 15 percent of couples in North America experience infertility. Identifying modifiable risk factors for infertility, including diet, could help couples conceive more quickly and reduce the psychological stress and financial hardship related to fertility treatments, which are associated with more than $5 billion in annual US healthcare costs. Through the Pregnancy Study Online (PRESTO), an ongoing web-based prospective cohort study of North American couples, the researchers surveyed 3,828 women aged 21 to 45 living in the United States or Canada and 1,045 of their male partners. Participants completed a comprehensive baseline survey on medical history, lifestyle factors, and diet, including their intake of sugar-sweetened beverages. Female participants then completed a follow-up questionnaire every two months for up to 12 months or until pregnancy occurred. Both female and male intake of sugar-sweetened beverages was associated with 20 percent reduced fecundability, the average monthly probability of conception. Females who consumed at least one soda per day had 25 percent lower fecundability; male consumption was associated with 33 percent lower fecundability. Intake of energy drinks was related to even larger reductions in fertility, although the results were based on small numbers of consumers. Little association was found between intake of fruit juices or diet sodas and fertility. "Given the high levels of sugar-sweetened beverages consumed by reproductive-aged couples in North America, these findings could have important public healthimplications," the authors concluded.

Dr. Dawn attacks anti vaccine arguments based on expected reactions that prove the vaccine works! Anti-parasite drug Ivermectin may be useful to treat COVID-19; New strategy for creating greatly needed new antibiotics; Certain microbiome bacteria such as Bacteroides fragilis increase the risk of breast cancer; Are neurotransmitter tests useful? Probiotics for IBS

Dr. Dawn attacks anti vaccine arguments based on expected reactions that prove the vaccine works! Anti-parasite drug Ivermectin may be useful to treat COVID-19; New strategy for creating greatly needed new antibiotics; Certain microbiome bacteria such as Bacteroides fragilis increase the risk of breast cancer; Are neurotransmitter tests useful? Probiotics for IBS

Welcome back to USMLE Listen This is MICROBIOLOGY Chapter 6: Enterobacteriaceae! Whether you're on a run or driving, this is The PERFECT podcast to initiate your auditory learning for the USMLE Step 1! In this episode, it's all about USMLE-important Gram Enterobacteriacaea Important exam related information on gram-negative bacteria in the ENTEROBACTERIACEAE FAMILY which include E.coli, Klebsiella, Shigella, Yersinia, Proteus, Salmonella, Haemophilus, Gardnerella, Pasteurella, and Bacteroides. We will also go over bacterial infections caused by ANIMAL AND HUMAN BITES as well as the different bacteria that cause ENDOCARDITIS! Review EACH USMLE critical Enterobacteriaceae: Features Transmission & Predisposing Factors Pathogenesis Diseases Associated Treatment Important to Know Info! As always, you can email us at USMLElisten@gmail.com for your questions, anything you need to be cleared, or suggestions on how we can improve and initiate your auditory learning for the USMLE Step 1. Sources for USMLE LISTEN include First Aid, Osmosis, Uworld, and Kaplan study guides. This is Mark Labella, you can follow or message me on Instagram at markjlabella. See you in the next episode for your auditory learning at USMLE LISTEN!

Microbiology- all about Bacteroides fragilis and tricks to remember the details --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.18.304071v1?rss=1 Authors: Narasimhan, R. L., Throm, A. A., Koshy, J. J., Saldanha, K. M. R., Chandranpillai, H., Lal, R. D., Kumravat, M., Kumar K M, A., Batra, A., Zhong, F., Liu, J. Abstract: Inflammatory bowel disease (IBD) is a complex, chronic inflammatory disease of the gastrointestinal tract with subtypes Crohn's disease (CD) and ulcerative colitis (UC). While evidence indicates IBD is characterized by alterations in the composition and abundance of the intestinal microbiome, the challenge remains to specify bacterial species and their metabolites associated with IBD pathogenesis. By the integration of microbiome multi-omics data and computational methods, we provide analyses and methods for the first time to identify microbiome species and their metabolites that are associated with the human intestine mucosal immune response in patients with CD and UC at a systems level. First, we identified seven gut bacterial species and seventeen metabolites that are significantly associated with Th17 cellular differentiation and immunity in patients with active CD by comparing with those obtained in inactive CD and non-IBD controls. The seven species are Ruminococcus gnavus, Escherichia coli, Lachnospiraceae bacterium, Clostridium hathewayi, Bacteroides faecis, Bacteroides vulgatus, and Akkermansia muciniphila, and a few associated metabolites include the secondary bile acid lithocholate and three short-chain fatty acids (SCFAs): propionate, butyrate, and caproate. We next systematically characterized potential mechanistic relationships between the Th17-involved metabolites and bacterial species and further performed differential abundance analysis for both microbiome species and their metabolites in CD and UC relative to non-IBD controls with their metagenomic and metabolomic data. Based on the deconvolution of immune cell compositions from host intestinal bulk RNA-seq, we investigated changes in immune cell composition and abundance in CD and UC in comparison to non-IBD controls. Finally, we further extended our species and metabolite associations with immune cells from Th17 and Th2 cells to B cells, plasma B cells, CD4+ T cells, and CD8+ T cells. While a set of associations of immune cells with bacterial species and metabolites was supported by published evidence, the new findings in this work will help to furthering our understanding of immune responses and pathogenesis in IBD. Copy rights belong to original authors. Visit the link for more info

  Welcome to episode 413 of The Whole View. On this week's episode, we talk about the benefits of eating nuts on the gut microbiome. Who knew that tree nuts had so many benefits?! All of this and more in episode 413!    If you enjoy the show, please review it on iTunes! The Whole View, Episode 413: The Gut Health Benefits of Nuts Welcome back to the Whole View, episode 413. (0:27) Stay tuned to the end to see Stacy's embarrassing blooper! When Stacy started Paleo 10 years ago, nuts were extremely popular, and then the "paleo police" got ahold of them and they became demonized for their caloric density and use in dreaded baked goods. But while moderating nuts is probably a good idea, they definitely do have their benefits! Brazil nuts have a huge amount of selenium for example. Today's sponsor is Georgia Grinders nut butters! Go to http://www.georgiagrinders.com/thewholeview/ and enter THEWHOLEVIEW for 25% off! Sarah found these nuts at her local farmers market way back 7 years ago when they only made almond butter. Now they're launching nationwide in Krogers! Now they do all kinds of nut butters! No added oils or sugars and  own and operate their own manufacturing facility We love the Pecan, Hazelnut and Cashew butters as well! What's Good About Nuts? Sarah has found nut research fascinating and surprising as the health community vacillates between love and hate (9:02) Peanuts account for 2/3 of American nut consumption despite actually being a legume (it grows underground, not on trees!) Peanuts have challenges: they're very pesticide heavy and are susceptible to mold. Most scientific studies can't separate out quality. Are the problems with peanuts problems with peanuts or quality? Is it the HFCS or hydrogenated oils perhaps? A mere 20 grams of tree nuts per day is associated with substantially reduced risk (think 20-70%) of cardiovascular disease, cancer, neurodegenerative disease, kidney disease, diabetes, infections, and mortality from respiratory disease. High fat plant based foods: nuts and seeds, olives and avocados. That's it! Nuts are unique because they have a lot of mineral content. High in polyphenol and phytosterol which lower cholesterol. High in Vitamin E and B vitamins as well.  Unique fiber types and fats that are good for gut microbiome. High in L-Argenine and L-Glutamine, which are essential amino acid they need to consume as well. These amino acids alone change the gut microbiome composition. These properties alone might account for why nuts have all these health benefits. Numerous studies show that people who regularly eat nuts tend to have more favorable blood lipid profiles, and one meta-analysis of 25 clinical studies showed that nut consumption had a dose-response cholesterol-lowering effect. Interventional studies consistently show that increasing nut intake has a cholesterol-lowering effect, even in the context of healthy diets. Plenty of research suggests that, despite their energy density, nuts and seeds don’t contribute to weight gain, and they may even protect against obesity and diabetes. This is probably because of their gut microbiome effects. "Our gut microbiomes basically control our biology. They're more influential on our biology than our brains. Everything about our health is intertwined with the gut microbiome." Read Sarah's Ebook, The Gut Health Guidebook! Different nuts have different Omega-3 to Omega-6 ratios, which is tied to cholesterol and cardiovascular health. But the heart benefits of nuts aren't tied to the ones best for that ratio. If that was the mechanism, than no nut should have that benefit because none had the most beneficial Omega-3s like seafood has. Most likely they are heart healthy because of monounsaturated fat. Nuts and seeds are an early reintroduction on AIP because their benefits far outweigh the reasons you would cut them out (essentially only because they have a high instance of intolerance). Stacy found that dose was important with her reaction to nuts and that quality was important. Don't oxidize your nuts by having them sit for months or buying cheap low quality nuts. Benefits of Walnuts Let's talk about the benefits of individual nuts that have been studied (29:44) Sarah is most interested in the mechanisms of provoking health, they "why?" of it. And she keeps seeing it linked back to gut microbiome benefits. Best studied nuts are walnuts, almonds and pistachios. In one randomized, controlled human trial, almost 200 healthy adults were given either eight weeks of a walnut-enriched diet (43 g of walnut per day) followed by a nut free diet, or the same two diets in reversed order. The study found that walnuts significantly increased the abundance of Ruminococcaceae and Bifidobacteria, while opportunistic Clostridium sp. cluster XIVa species species significantly decreased. Overall, walnut consumption appeared to give a major boost to probiotic and butyric acid-producing species in the human gut. Another study tested the effects of eating either 42 g of walnuts or 0 g of walnuts daily for three weeks, and found that walnut consumption resulted in a 49-160% increase in the relative abundance of Faecalibacterium, Clostridium, Dialister, and Roseburia, while also causing a 16-38% lower relative abundance of Ruminococcus, Dorea, Oscillospira, and Bifidobacterium. Likewise, compared to the walnut-free diet, the walnut diet reduced the microbially derived, proinflammatory secondary bile acids deoxycholic acid and lithocholic acid by 25% and 45% respectively, coinciding with a reduction in LDL cholesterol. The researchers concluded that the gut microbiota may play a direct role in some of the health benefits associated with walnuts! In rats, a similar study feeding walnuts versus a macronutrient-matched walnut replacement (corn oil, casein, and cellulose fiber) found that walnuts enriched the microbiota with probiotic bacteria including Lactobacillus, Ruminococcaceae, and Roseburia, while also significantly reducing Bacteroides and Anaerotruncus. Benefits of Almonds Because almonds are one of the highest Omega-6 nuts, they're often considered "the worst nut"  but in terms of the gut microbiome, they're fantastic! (38:43) They've compared defatted almonds and skinned almonds, but really the benefit seems to be from the fiber improving species diversity. The more species you have, the more cooperation between species. For example, creating B12 has 30 different processes and it takes many bacteria cooperating to form B12 in the gut. And more species mean less opportunity for the opportunistic bacteria to take over. A study of college freshmen found that eight weeks of almond snacking (vs. graham crackers) (56.7 g per day of almonds) led to a significant increase in microbiota α-diversity and a 48% decrease in the abundance of the pathogen Bacteroides fragilis. In another study, 48 adults were fed a daily dose of 56 g of roasted almonds, 10 g of almond skins, or 8 g of just the fiber as a control.  After six weeks, fecal levels of bifidobacteria and lactobacilli were significantly higher from consumption of both the almonds and almond skin, while levels of Clostridum perfringens significantly decreased—suggesting components of the almond skins (present both in whole almonds and the skin only) were responsible for these prebiotic effects. Stacy heard someone redefining how you should think of macronutrients as protein fat and fiber instead of protein fat and carbohydrates, because it's the fiber that will be the health benefits. Sarah agrees the fiber targets are a good idea because fiber is often neglected and is very important. Fiber is carbs we can't digest but our microbiome can! And small changes to fiber molecules mean that some species can break it down and some can't. So variety in fibers is important for species diversity! The Benefits of Pistachios Pistachios are different from other tree nuts. They're in the cashew family (same as poison ivy and mango, actually!) (50:18) They definitely contribute to diversity of gut microbiome species like other nuts. Uniquely, they also reduced the levels of trimethylamine N-oxide (TMAO) measured in the urine. TMAO is the byproduct that is the link between red meat and cardiovascular disease. (though it is unknown whether it's a gut microbiome issue that produces it or if the TMAO causes the bad microbiome).  Other Nut Benefits Sarah is going to hit you with her fun facts! (53:19) Every nut and seed that has been evaluated in terms of its impact on the microbiome shows unique benefits. That means variety is best! Hazelnuts and pecans have the highest proanthocyanidin (an awesome class of polyphenols) content Highest contents of ellagic acid (walnuts and pecans) also presented the highest total phenol contents Macadamias and cashews are the highest in monounsaturated fats (also good for microbiome, and heart-healthy) Brazil nuts are super high in selenium, like 1 has 175% of the RDI! And an ounce has 1000% of the RDI! Selenium is important for immune and brain function. And it's why you go crazy from mercury because it permanently binds with selenium. Hatters should have been pounding brazil nuts!  And Ounce per Day! An ounce of nuts per day is the best idea. No further benefits after about an ounce. (58:26) Moderation is a "dirty word" in health communities because people use it to rationalize less than ideal choices. But in terms of nuts, this actually is the best option. Going beyond that can increase risk of stroke. So don't go nuts on nuts! Stacy thinks of it in terms of how our ancestors would have eaten them. They're time consuming to get out of the shell and last longer than fruits and vegetables, so moderation seems like what would have been our relationship to them. While there are some primates that do eat nuts as a primary food source. Sarah is curious how these species have adapted to high nut lifestyles. Closing Thoughts A huge thank you to Sarah for pulling all of the science together. (1:04:12) Send us more questions through the contact form on the website. Thanks for listening Thanks to Georgia Grinder and their nut butters (Peanut, Almond, Hazelnut, Pecan and Cashew)! Go to http://www.georgiagrinders.com/thewholeview/ and enter THEWHOLEVIEW for 25% off! Handcrafted in small batches in their own facilities, no added sugars or oils or other problem ingredients. Just top quality nuts! We will be back again next week. Thank you again for listening. (1:07:05)  

Welcome to the Whole View, episode 406. (0:27) Stacy is so jazzed about this show. Sarah and Stacy have been talking about it and preparing for it since this show was called the Whole View. Stacy personally is jazz hands about educating a dear loved one on why filtering water is a good idea. To kick things off, Stacy is going to share a little story from their trip last summer. While on the road, Stacy saw what she thought was a fresh spring and encouraged the boys to fill their water bottles. Stacy basically gave her kids dysentery. This is Stacy's story about why water filtration is important. Stacy ran a poll last week and only 21% were on team Stacy and thought it was a harmless stream. What Stacy thinks is fascinating is that it is not just runoff water that is not good for you. Oftentimes our municipal water is not meeting the standards. It is important to understand that, and beyond that, it is important to know what you should be aware of when it comes to water. Sarah has so much science.   This Week's Sponsor But first, Stacy wants to take a moment to thank this week's sponsor, AquaTru. (4:27) Their reverse osmosis system has been sitting on Stacy's counter for a month now, but there is one person in the house who is not convinced that it is a good idea. Stacy first loved this system because of the information that Sarah shared, but second loved that it is endorsed by Erin Brockovich. Sarah has had an AquaTru for over four years, and what she loves about them is how different their technology is. It’s the only counter-top reverse osmosis system —  in a category all its own. It is not bottled water, not a fridge filter pitcher like Brita or Pur, and is not an under the counter or whole house system needing installation. AquaTru is the only purifier to remove the ‘forever chemicals’ known as PFOAs and at the center of the movie Dark Waters. Most reverse osmosis (RO) systems waste four gallons of water for every one gallon they produce. AquaTru uses a patented water conservation technology that is about 12x more efficient than professionally installed under-the-sink RO systems. RO is the best way to filter water. They are giving our podcast listeners $150 off their AquaTru purchase.   Listener Question Jessica says, "new podcast name! Love it! (10:44) Thanks for continuing to podcast. Crazy times in the world and you and Sarah’s voice is so utterly comforting. Anyway, podcast question! Water intake. I don’t think you guys have done a, 'how much water do we need', podcast episode. A deep dive into this would be really helpful. The standard advice seems to be either one amount for men and one amount for women, or, half your body weight in oz.  Which is correct? Or is there another answer? What about just drinking when thirsty? I also have wondered, how much water did our ancestors drink? I assume the water was maybe harder to come by back then so maybe they were drinking less? This is the assumption I’ve always made and has led to me drinking intuitively, which has more than likely led to me being chronically dehydrated :) I feel like with all the conflicting info, it would be great to hear the science.  By the way Stacy, as a side note, after about a year I finished catching up on the podcast. I know you are sorry, I am not ;). When searching for a water-related episode, I and came upon an episode called Thirsty Brain. I was like, for sure this has to be about how water intake affects our brain. Nope. Lol. But that was a great episode about Matt’s podcast, called Thirsty Brain :) love you guys.   Thanks again for all you do!"   How Much Let's start with how much water. (14:15) This has been a debated topic within the medical and scientific community. The classic 8, 8 oz. glasses a day is actually not enough. However, this original recommendation was based on how much water we lose over the course of a day and was not based on how much we actually need. The question now is, how much water makes us healthy? The latest research suggests that men should consume about 13 cups (104 ounces, or 3 liters) of fluid per day, and women should consume about 9 cups (74 ounces, or 2.2 liters). The reason it is different between men and women is basically a reflection of body size and BMR. This amount is not pure water intake. It includes the water that we get from all sources, factoring in all beverages, and the water we get from food. From there, our needs would shift up if we are highly active, if it is hot out, certain dietary needs, etc. Sarah thought the hunter-gather aspect of Jessica's question was very interesting. So she spent some time trying to track that information down. However, she couldn't find a good estimate. That being said, Sarah did find a really interesting paper looking at human evolution. We only find remains of early humans near water sources, and so we know that early humans tended to congregate near water. Communities were and still are centered around ways of getting water. There has been some anthropological research showing that this might have been very important in human evolution. Our brains use a lot of energy, which creates a lot of metabolic byproducts, which have to be filtered by the liver and kidneys, which increases our need for water to make urine to effectively detoxify. So our ability to grow these awesome brains would have relied on proper hydration, in addition to high-quality food. We can't say how many ounces of water hunter-gathers consumed on average, but we can say that it was very likely that they drank a lot of water and likely drank intuitively.   Intuitive Hydration Studies looking at hydration have been really interesting. (19:56) Overall they show that humans in general as a species are pretty good at drinking intuitively. Studies have come at this from a bunch of different ways, where they have looked at what happens when you have given people free access to water and you measure how much water they drink? In general, people are really good at staying hydrated, provided water is around. On average people will drink about two liters of water per day, just driven by thirst. Which is probably the right amount of water, considering other beverages and water from food sources. There have been studies showing that this is true in different populations. Athletes' performance is best when they just follow their thirst for drinking. 'Follow your thirst' does seem to work best for performance. However, there are a variety of things that have been shown to reduce our thirst relative to our water needs. Which basically means you are not thirsty enough for how much water you need. These people need to focus more on hydration and drink with intention, versus just following thirst. There are a bunch of drugs that are used for cardiovascular disease that impact thirst. Elderly people also tend to end up dehydrated and are do not have strong enough thirst signals for their water needs. Menopause causes this is women and high estrogen in general. Swimming can actually reduce our thirst. Exercising in the heat can also impact our thirst awareness. When Sarah looks at this list this means that there are so many exceptions that overall it is a pretty good idea to at least be mindful of hydration. There are bad things that happen when we don't drink enough water on a regular basis. Stacy shared her experience with her lack of thirst and dehydration.   What Happens if you Don't Drink Enough? What is interesting is that acute dehydration will make you feel extremely ill, but chronic-mild dehydration kind of creeps up on you in terms of the symptoms. (27:03) Like so many chronic things, the human body is remarkable in terms of how it adapts to not feeling good. You can end up not noticing for a while. There has been a huge variety of studies showing that even mild dehydration puts a strain on the kidneys, which can cause high blood pressure, reduced energy, fatigue, constipation, dry skin, and more. What is interesting to Sarah is the number of cognitive issues associated with mild dehydration. It can cause frequent headaches, impair mood, increase anxiety, reduce concentration, impair memory, reduce cognitive performance and it also has a pretty measurable impact on exercise performance. The thing that nerds Sarah out is that our microbiome is sensitive to our hydration status. This is because we have this whole collection of bacterial species that actually live in or attached to the mucus barrier. Sarah explained the mucus layer in greater detail. This is why inadequate hydration can cause constipation. What happens when we are not drinking enough, that the mucus layer gets harder and less viscus. This makes it a less hospitable environment for really important probiotic bacteria. It also makes it a more hospitable environment for pathogens. This has been confirmed in some really interesting animal studies. Acute hydration would include feeling dizzy, rapid heartbeat, rapid breathing, extreme fatigue and sleepiness, confusion, and irritability and it can cause things like fainting. You would see severe dehydration in having UTIs, kidney infections, and kidney stones.   Alkaline Water Sarah feels that alkaline water is one of the biggest scams in the health community. (34:48) Alkaline water has an alkaline pH. Commercial alkaline water typically has a pH of 8.8 or higher with high dissolved mineral content, typically calcium, potassium, and magnesium. Alkaline water is known to neutralize stomach acid, which on the surface may sound like an awesome thing for anyone who suffers from acid reflux. However, because the acidity of chyme is a key signal to the pancreas to secrete digestive enzymes and to the gallbladder to secrete bile, neutralizing stomach acid can hinder digestion in a big way! So anything that neutralizes stomach acid actually hinders digestion, which can cause a whole pile of problems. The other thing is the impact on the gut microbiome. If you are neutralizing those acidic molecules with alkaline water, you are actually suppressing the growth of really key probiotic species and increasing the growth of potential pathogens. Studies confirm that drinking alkaline water causes an undesirable shift in gut microbiome composition. One study in mice showed that drinking alkaline water for 4 weeks caused a huge decrease in probiotic Clostridiumspecies with smaller decreases in Bifidobacterium and Lactobacillus, and a rise in Prevotella. A randomized, controlled cross-over intervention in adult men compared the impact on the gut microbiome of consuming 2 liters per day of alkaline water (pH 9) compared to neutral water (pH 7) for two weeks. While the alkaline water had no effect on overall species diversity or richness, the men benefited from higher hydration levels from neutral pH water, which significantly increased richness by 15% when comparing pre- and post-intervention samples. The benefits of alkaline water that have been measured are probably completed attributed to the fact that many of us are not getting enough calcium or potassium. So we can benefit from getting these in their elemental form dissolved into water.   Spring Water Spring/mineral waters can be slightly acidic. (38:50) Most natural sources of mineral water in the world are acidic, not alkaline. Acidic water, because our gut bacteria love living in an acidic environment, has been shown to improve the gut microbiome to reduce a diabetes-associated microbiome. It also improves the growth of probiotic species, at least in animal studies. So it is much more important to look for mineral water or to add mineral drops to your water. Sarah adds mineral drops to her water before she drinks it. There is definitely benefit to mineral content, but that alkaline water is not doing your gut any favors. Stacy has experienced this with the digestive piece before.   Tap Water The water that comes out of our taps originates from lakes, rivers, and or groundwater. (41:37) Then it goes under extensive filtration and then disinfection. Disinfection uses one of two chemicals - chlorine or chloramine. It is important for safety to go through this disinfection process. When you think about the community of microbes that live in our gut and think about a disinfectant being added to our water, you think about the impact this has on your gut bacteria. Studies have shown that they absolutely do. The chlorine/chloramine that is added to drinking water not only decreases the growth of really important probiotic species, but it actually allows the growth of multi-resistant pathogens. There have been a variety of studies showing that feeding animals chlorinated tap water actually increases the number of bacteria that are growing in their digestive tract. These bacteria strains are associated with hospital inquired infections. Studies have shown that there is a potential link between chlorinated drinking water and the incidence of colorectal cancer. To understand whether this effect is mediated via the microbiome, a study compared the effect of drinking chlorinated water versus tap water in transgenic mice susceptible to colon cancer. Chlorinated water causes a substantial increase in tumor development in the colon, associated with reduced levels of Clostridium perfringens, a species believed to have anti-tumor effects. Interestingly, mice drinking tap water tended instead to develop tumors in the small intestine. Removing the chlorine/chloramine after the water comes out of our tap before we drink it, is a really good idea for our gut microbiome.   More on Fluoride There are also a lot of municipalities in North America that add fluoride to tap water, with the rationale of reducing tooth decay. In episode 34 Stacy and Sarah discussed fluoride, and the science has not changed. The science showing that fluoride is beneficial for dental health when it makes prolonged contact with tooth surfaces is really strong. However, the science showing any benefit to oral health from drinking fluoridated water is basically nonexistent. There have been some really large studies showing that fluoridation does not increase the risk of anything of the things that have been rumored to be true. However, there have been a few studies showing a correlation between fluoride levels and lower IQ in children. This has opened up the question if fluoride can open up the blood-brain barrier, and potentially negatively impact early brain development. But this is still a big open question where more science is needed. We do know that fluoride seems to accumulate in the pineal gland as we age.  The pineal gland is located in our brain and secretes melatonin to help us sleep. We don't know if this is what is behind sleep disturbances, but its something to point to that shows how fluoride crosses the blood-brain barrier. Overall, more research is needed to clarify if there are actual risks with fluoridation. We do know that the benefits are not measurable. In a study of broiler chickens, high levels of dietary fluorine resulted in lower microbial diversity, significantly lower levels of Lactobacillus and Bifidobacterium species. The study also showed significantly higher levels of Escherichia coli and Enterococcus compared to the control group. In a mouse study, 12 weeks of exposure to fluoride altered the oral microbial community by selectively depleting probiotic Parabacteroides distasonis, Bacteroides uniformis, and an unclassified Bacteroides species. However, if we are using fluoridated toothpaste, drinking non-fluoridated water appears to pose no risk to oral health. There is a strong case for filtering water for removing chlorine, chloramine, and fluoride. Stacy isn't yet adding minerals to her water but is going to give it a try and is excited. You can get those minerals on the AquaTru.   Pesticide Residues in Tap Water While an inexpensive activated carbon (charcoal) water filter can remove chlorine, chloramine, and fluoride from tap water. Unfortunately, these common water filtration systems can’t remove pesticide residues. Heavy metals are a well-known problem. (53:57) If you have lead in your tap water there is so much information out there that you would understand the importance of not showering in this level of contaminated water. We talked about how glyphosate impacts the gut microbiome in last week’s episode (405). Glyphosate exposure increases the ratio of pathogenic bacteria to probiotic microbes, reducing Bifidobacteria, Lactobacillus, and Enterococcus while increasing Salmonella and Clostridium. There is no dose-response. Any glyphosate exposure is problematic. In the US, glyphosate has been used for over 40 years and is used mostly to kill weeds that interfere with agricultural crops (typically corn, soy, and canola). We know that runoff from industrial agriculture is a major source of contaminants in streams, rivers, and lakes, which is where we get our tap water from. Third-party testing was done on 85 tap water samples by Moms Across America and Sustainable Pulse. The results showed that 35 of the samples had glyphosate levels up to 0.3 ppb. On average, 87% of Americans have measurable glyphosate residues inside their bodies. For more on how glyphosate impacts our health, see this study. We know we are getting exposed to glyphosate and it looks as though tap water may be a key root of exposure. This is the most compelling reason for filtering water using reverse osmosis.   Closing Thoughts Sarah is so grateful for AquaTru for giving our listeners such a steep discount on their filtration systems. Last week we talked about foundational principles, and Sarah considers filtering water as a foundational principle. Reverse osmosis is the next level thing. However, depending on where you live, if you live in an area where your water is likely to be contaminated, that shifts that priority. Stacy and Sarah are on a mission to educate, they never want to make listeners feel burdened with one more thing to worry about. Instead, you make informed decisions from education and we are here to educate you. Stacy doesn't want someone to spend a lot of money on a water filtration system without looking fully into the research and which system to buy. It is fascinating to Stacy that this is beyond heavy metal contamination, it is beyond glyphosate, that three out of four homes have contaminants beyond the prescribed measures in America. This was a fact that once she heard it, Stacy couldn't un-hear it. Is this a burden that you should be stressed out about - absolutely not. This is to educate you so that you can plan for if you want to make changes. A great place to start is to look at what is in your water. Use this site as a reference point. For you to be aware and to start looking at that is all that we are trying to provide. If you are concerned about your water quality and do feel like a good water filtration system is a good investment to make, AquaTru has given our listeners $150 off. Simple visit this site to get that discount. Sarah wanted to thank AquaTru again for sponsoring this week's episode and for being such a good sponsor to provide listeners with such an amazing discount. Thank you listeners for being a part of the show. We love hearing from you and your feedback. Jessica, thank you for your nice complement. If you have questions that you want us to follow up on or different topics that you want to hear about, we welcome you to email us using the contact forms on our blogs. Please engage with us on social media. If you learned something from listening to one of our shows, the best thing you can do is share about it. Please also leave a review in whatever platform you are listening to. Thank you so much, listeners! We will be back next week. (1:05:22)

Časovnica: [00:00:55] O projektu nadaljnjega izobraževanja o prehrani, vadbi in kritični presoji literature. Kultura pogovora preko socialnih omrežij ter epilog poizkusa svetovnega rekorda v mrtvem dvigu. [00:19:35] Inteligenca in kritično razmišljanje nista ista stvar. Zakaj pametni ljudje počnejo neumnosti. Zakaj je kritično razmišljanje ključ do dobrega življenja. [00:31:25] Kofein kot dopolnilo za izboljšanje zmogljivosti ter kako genotip vpliva na časovni vnos kofeina. [00:44:25] Vpliv mikrobiote in probiotikov na hujšanje. Visok vnos vlaknin in nižji vnos maščob za optimalno zdravje prebavil. [01:15:05] Zakaj vzdržljivostni športniki potrebujejo več beljakovin. [01:22:45] Zaključek.   Omenjeni članki: Zakaj pametni ljudje počnejo neumnosti: Why Do Smart People Do Foolish Things: https://www.scientificamerican.com/article/why-do-smart-people-do-foolish-things/ Vpliv genotipa na jemanje kofeina: Grgic et al. CYP1A2 genotype and acute effects of caffeine on resistance exercise, jumping, and sprinting performance. J Int Soc Sports Nutr 17, 21 (2020). https://doi.org/10.1186/s12970-020-00349-6 Mikrobiota in hujšanje: Fragiadakis. et al. (2020) ‘Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight', The American Journal of Clinical Nutrition. Oxford University Press, pp. 1–10. https://doi.org/710.1093/ajcn/nqaa046  Hjorth et al. (2018) ‘Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention', International Journal of Obesity. Nature Publishing Group, 42(3), pp. 580–583. https://doi.org/10.1038/ijo.2017.220 Višji vnos vlaknin in nižji vnos maščob za optimalno zdravje prebavil: O'Keefe et al. (2015) ‘Fat, fibre and cancer risk in African Americans and rural Africans.', Nature communications, 6(May 2014), p. 6342. https://doi.org/10.1038/ncomms7342 Le Leu et al. (2015) ‘Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: A randomised clinical trial', British Journal of Nutrition, 114(2), pp. 220–230. https://doi.org/10.1017/S0007114515001750 Meta-analize o učinkovitosti probioikov pri hujšanju: Mazloom et al. (2019) ‘Probiotics: How Effective Are They in the Fight against Obesity?', Nutrients, 11(2), p. 258. https://doi.org/10.3390/nu11020258 Mohammadi et al. (2019) ‘Effects of pro-/synbiotic supplementation on anthropometric and metabolic indices in overweight or obese children and adolescents: A systematic review and meta-analysis', Complementary Therapies in Medicine. Elsevier Ltd, 44, pp. 269–276. https://doi.org/10.1016/j.ctim.2019.05.008 Cao. et al. (2020) ‘Effect of probiotic and synbiotic formulations on anthropometrics and adiponectin in overweight and obese participants: A systematic review and meta-analysis of randomized controlled trials', Journal of King Saud University - Science. The Author(s). https://doi.org/10.1016/j.jksus.2020.01.011 Potrebe vzdržljivostnih športnikov po beljakovinah: Kato et al. (2016). Protein Requirements Are Elevated in Endurance Athletes after Exercise as Determined by the Indicator Amino Acid Oxidation Method. PloS one, 11(6), e0157406. https://doi.org/10.1371/journal.pone.0157406 Bandegan et al. (2019). Indicator Amino Acid Oxidation Protein Requirement Estimate in Endurance-Trained Men 24h Post-Exercise Exceeds both the EAR and Current Athlete Guidelines. American Journal of Physiology-Endocrinology and Metabolism, 316(5):E741-E748. https://doi.org/10.1152/ajpendo.00174.2018   Sledite nam: Nenadov instagram: @nenad.feelgood Matjažev instagram: @matjaz.feelgood Feelgood Skupnost na Facebooku: https://bit.ly/feelgoodskupnost Spletna stran: https://www.feel-good.si   Poslušate nas lahko na: Podbean: https://bit.ly/podbean-zdp Stitcher: https://bit.ly/stitcher-zdp Pocket Casts: https://bit.ly/pocket-zdp Podcast Addict: https://bit.ly/addict-zdp Castbox: https://bit.ly/castbox-zdp iTunes: https://bit.ly/itunes-zdp  

  This month on Episode 111 of the Discover CircRes podcast, host Cindy St. Hilaire highlights three featured articles from the March 27 issue of Circulation Research and talks with Dr. Matthias Nahrendorf  and Dr. Maximilian Schloss about their article Modifiable Cardiovascular Risk, Hematopoiesis and Innate Immunity.   Article highlights:   Liu et al. Genetics of Transposition of the Great Arteries   Park et al. Mild Lipid Abnormalities and ASCVD in the Young Yan, et al. Gut Flora Adjusts Blood Pressure By Corticosterone Transcript Cindy St. Hilaire:              Hello and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh. Today, I'm going to share with you articles selected from the March 27th issue of Circulation Research, as well as give you a hint of the cutting-edge ideas in the Compendium on atherosclerosis. We'll also have a discussion with Dr Maximilian Schloss and Matthias Nahrendorf about their article On Modifiable Cardiovascular Risk, Hematopoiesis And Innate Immunity. So, first the highlights.                                            The first article I'm sharing with you is titled Exome-Based Case Control Analysis Highlights the Pathogenic Role of Ciliary genes and Transposition of the Great Arteries Exome-Based Case-Control Analysis Highlights the Pathogenic Role of Ciliary Genes in Transposition of the Great Arteries. The first authors are Xuanyu Liu and Wen Chen and the corresponding author is Zhou Zhou from Peking Union Medical College in Beijing, China. In normal healthy hearts, the aorta develops from the left ventricle and the pulmonary arteries from the right ventricle, but in the common congenital heart malformation called transposition of the great arteries or TGA, the plumbing of these two major vessels is switched. Thus, the pulmonary arteries arise from the left ventricle and the aorta from the right.                                            This is a life-threatening condition, requires surgery in the earliest days of life and currently, the genetic etiology of this congenital disease is largely unknown. To identify the genetic drivers of transposition of the great arteries, the authors of this study performed whole exome sequencing of 249 TGA patients and, in 66 cases, they were actually able to do exome sequencing on their parents as well. The analysis identified 82 candidate genes in which the allele variant or mutation that was found in TGA patients was predicted to alter protein function.                                            Interestingly, a quarter of these mutations or variants were found to be in genes that are involved in cilia function. So, the cilium is an organelle that's found on all eukaryotic cells and is in the shape of a slender protuberance that projects from the much larger cell body. Recently, cilia have been identified as playing a central role in the pathogenesis of congenital heart diseases, and it has been suggested that congenital heart disease may be a new class of ciliopathy. Transposition of the great arteries has been hypothesized to arise from disturbances in the left right patterning during embryo development, and cilia are required cellular organelles and they are essential for left-right axis determination in early development. These findings add to the growing body of evidence that has identified a role of cilia genes and congenital heart disease and may lead to future prenatal diagnostic screenings.                                            The next article I want to highlight is titled Mildly Abnormal Lipid Levels, but Not High Lipid Variability, Are Associated with Increased Risk of Myocardial Infarction and Stroke in ‘Statin-Naive’ Young Population: A Nationwide Cohort Study. The first author is Jun-Bean Park and the corresponding author is Hyung-Kwan Kim from Seoul National University Hospital in Seoul in the Republic of Korea. High levels of lipids in the blood increase a person's risk of cardiovascular disease, and evidence suggests that this risk builds over lifetime. However, in young adults, and in this case, young adult means any individual between 20 and 39 years of age. In young adults, relatively little evidence is available that identifies individuals at high risk for atherosclerotic cardiovascular diseases, except for very high LDLC levels.                                            Variability in lipid levels has recently emerged as a predictor of adverse clinical outcomes and lipid level variability may be causally linked with the atherosclerotic cardiovascular disease risk. This is because theoretically, high lipid levels can induce fluctuations in the atherosclerotic plaque composition. These fluctuations result in plaque instability and rupture and ultimately, plaque related clinical events, such as myocardial infarction. However, high lipid level variability may merely reflect other risk factors or confounders for atherosclerotic cardiovascular diseases, including unhealthy lifestyle and unrecognized comorbidities. This study therefore examined health data of close to two million Korean individuals aged 20 to 39. None of them had ever been treated for high cholesterol with statins nor had any of them suffered any myocardial infarctions or stroke.                                            Over a four-year period, the subjects had undergone at least three lipid measurements as part of their general health assessments and then they were followed for a further four years or until death. The data showed that high baseline lipid levels was linked with an increased risk of adverse cardiovascular events, and in particular, myocardial infarctions. They also found that individuals who exhibited high lipid variability, so sometimes getting high readings, sometimes getting low readings, these individuals who exhibited high variability and lipid level measurements were not at any greater risk of such cardiovascular events. While such up and downs have previously been linked to cardiovascular disease, this study argues that perhaps statin use in other cohorts may have contributed to the variability and thus confounded research interpretation, an issue that was specifically avoided in this study. Together the results indicate that lipid in young adults can indeed indicate future cardiovascular risk and therefore suggest lipid-lowering strategies could be beneficial for this age group.                                            The next article I want to share with you is titled Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension. The first author is Xuefang Yan and the corresponding authors are Zhe Wang and Qunye Zhang from Shandong University in China. Hypertension is highly prevalent in the adult population all over the world and it is a major risk factor for heart disease and stroke. A high salt diet can help to drive hypertension pathogenesis, but complete details about the mechanisms by which high salt intake shapes vascular pathology are lacking.                                            Recent studies show that fecal transfer from salt hypertensive to salt normotensive animals can lead to hypertension in the recipients, and this suggests that perhaps gut flora may play a role in hypertension. In the article by Yan and colleagues, they show that rats on a high salt diet have altered gut flora profiles and in particular that levels of the bacterium, Bacteroides fragilis, was reduced. Analysis of intestinal metabolites and substrates in high salt diet fed rats also showed that levels of arachidonic acid, which is produced by this bacterium, were low and levels of the stress hormone, corticosterone, which regulates blood pressure, were elevated.                                            The team went on to show that supernatants from this bacterial culture could prevent corticosterone production in the intestinal tissue of high salt fed mice as could direct treatment with arachidonic acid. Moreover, both B. fragilis and arachidonic acid were found to be lower in the feces of humans with hypertension compared to that of healthy controls. The results suggest B. fragilis and arachidonic acid normally curb corticosterone production and could therefore be novel targets for hypertension treatment strategies.                                            The last thing I want to mention before we switch to our interview is the Circulation Research Compendium on Atherosclerosis. The last compendium on this topic was back in 2016 and this new compendium provides the most cutting-edge ideas in the field. The topics highlighted in this compendium are polygenic scores to assess atherosclerotic risk, clinical perspectives, and basic implications, epigenetic reader proteins and cardiovascular transcriptional programs, sex as a biological variable in atherosclerosis, neutrophil extracellular traps in cardiovascular diseases, CD31 as a therapeutic target in athero, interleukin-1 and the inflammasome as therapeutic targets in cardiovascular disease, non-coding RNAs in vascular diseases, intracellular aspects of macrophage immunometabolism in atherosclerosis, single cell RNA sequencing in atherosclerosis, vaccination strategies and immune modulation in atherosclerosis and we have an update from the group leading the One Brave Idea. Please check out this compendium.                                            All right. So, now we're going to switch over to our interview portion of the podcast. I have with me today Dr. Matthias Nahrendorf, who is a professor at the Center of Systems Biology at Massachusetts General Hospital Research Institute and Harvard Medical School and his research fellow, Dr. Maximilian Schloss. Today, we're going to be discussing the article Modifiable Cardiovascular Risk, Hematopoiesis, Innate Immunity, which is part of our Compendium on Atherosclerosis. Circulation Research puts together two to three compendiums annually and this current one is the Compendium on Atherosclerosis. We will have two additional compendiums planned for 2020. One on Obesity, Metabolic Syndrome and Cardiovascular Disease and that should come out in late May and another on Atrial Fibrillation scheduled for June. So stay tuned.                                            So, thank you very much for being with me here today, Matthias and Maximilian. Matthias Nahrendorf:    Thanks for having us. Maximilian Schloss:        Thanks for having us. Cindy St. Hilaire:              So, I really enjoyed this review article. I actually learned a lot. I also really liked your cartoons at the end, so maybe we can talk about those a little bit later, but what it's on is essentially the role of inflammation and cardiovascular disease and years of study, which have recently culminated in the completion of the CANTOS trial, have showed us that reducing inflammation can help reduce cardiovascular events. When we look at the factors that we know drive cardiovascular disease, it's things like bad diet choices, lack of exercise, stress, and inadequate or disrupted sleep and in this article you make the more nuanced argument that these modifiable factors are in fact influenced by the innate immunity. So, before we dig too deep into what you are really discussing in this article, could you maybe give us a brief introduction to the role of innate immunity and cardiovascular disease initiation and progression? Matthias Nahrendorf:    Sure. Yeah. So, I think one very instructive experiment that had been done by more than one lab actually almost two decades ago, is stopping innate immune cells from migrating to atherosclerotic plaque by deleting the chemokine MCP-1 or the chemokine receptor CCR2 in mice that have a propensity to develop atherosclerosis. What became apparent is that these mice, despite having very high blood cholesterol levels, they don't really develop atherosclerosis. This really led the whole field now almost 20 years ago, to the insight that it's not only the hypercholesterolemia, it's also the immune system that contributes to the disease. So, innate immune cells, most numerous neutrophils and monocytes then in tissue also macrophages and they're meant to defend us against infections and they support healing. In this particular setting, they are probably doing more harm than good because they promote inflammation in areas where inflammation shouldn't be i.e., in the vessel wall. Maximilian Schloss:        Yeah, I would add that what Matthias said is that basically it's all about a balance between necessary inflammation and too much inflammation. If we take, for instance, myocardial infarction as an example, we need a certain amount of inflammation, local inflammation. We need a recruitment of innate immune cells like neutrophils and monocytes and eventually macrophages, to do their job. For instance, phagocytizing a dying cardiomyocytes or inducing fibrosis. So in this example, we need inflammation, but what we see in different models where we can manipulate inflammation being at reducing or increasing inflammation, we can see that if we do either/or then wound healing and scar formation is impaired. I think that's all we are interested in studying not only the mechanisms, how inflammation can be increased or decreased, but also what is actually the perfect balance in view also of finding ways of improving outcomes in cardiovascular patients. Cindy St. Hilaire:              One of the things in my research, so I focus on cardiovascular calcification, which is very hard to do in a mouse. They don't like to calcify similarly like they don't like to make plaque without a proper genetic background. Are there aspects of the mouse versus the human innate immune system that are very different? I mean I know specific receptors are slightly different, but in general, are they matched up pretty well or is there things that are quite different about them? Matthias Nahrendorf:    I think the answer is both and there are very important parallels and then there are very important differences. So, one important difference is just if you look at sheer numbers and the contribution of immune cells in the blood and, possibly also in the plaque, can be quite different. So, recent studies that use unbiased profiling in human plaques, for instance, say that there's quite a lot of lymphocytes and we still have to understand whether this is due to the retrieval or if it says species difference or the situation, but I think there are important differences. On the other hand, I think that it really make sense to study mice because a lot of the important discoveries about the immune system in the setting have translated to humans. Cindy St. Hilaire:              Like the IL-1 beta story. Matthias Nahrendorf:    That's right. Yeah. Cindy St. Hilaire:              So, actually one of the topics that you started out with in your article is on the role of hematopoiesis in cardiovascular disease. You had a beautiful paper years ago actually with my colleague at University of Pittsburgh, Partha Dutta, who's right down the hall from me, where you guys showed that myocardial infarction itself further exacerbates atherosclerotic plaques mid part through recruiting monocytes from the spleen and mobilizing the immune system. So, I'm wondering, what are the role of the cells when they get mobilized? You talk about these modifiable risk factors of stress and sleep interruption, unhealthy diet. So, how can these risk factors help or promote this mobilization of hematopoietic cells? Matthias Nahrendorf:    Yeah. So, I think that early on when we thought about going down this road and studying these risk factors, even before going there, you realize that the cells that we're interested in, innate immune cells are very short lived. So they live on the order of hours or days. So, they're really produced just in time. That's different to lymphocytes and resident macrophages, which have much longer lifespans. So, this really triggered the insight that we should look at production and release because it's a just in time supply situation. So, what we were wondering is whether in the setting of cardiovascular disease, whether production rates are increased and we now know and a number of labs have studied hematopoiesis in this setting including Fil Swirski, Alan Tall, and some others.                                            We now know that this is really the case, so hematopoiesis increases in chronic atherosclerosis. It increases in acute myocardial infarction and increases in heart failure. What we don't know is what mechanisms actually ramp up blood cell production and we're beginning to understand that the sympathetic nervous system is involved. But I think we only see the tip of the iceberg here. That's why we wanted to study modifiable risk factors, because if you look at others such as high cholesterol, once the insight was gained that lowering cholesterol is helpful, we had the statins which make a huge change. So, we hope to repeat that. Cindy St. Hilaire:              Maximilian, one of the things that you brought up is this balance. The inflammation's a little bit good and then it's a little bit bad or a lot bad. So, where is that good and bad spectrum in terms of mobilizing hematopoiesis or hematopoietic cells? Maximilian Schloss:        Yeah. I think that depends a bit on the disease type or we're talking about a chronic disease or an acute disease? For instance, to stay at the example of myocardial infarction, once cardiomyocytes become ischemic, they will release certain chemokines and cytokines into the blood, which then circulate to the bone marrow and tell the cells that leukocytes need to leave the bone marrow to enter the blood circulation system and then go to the heart to fulfill their very important functions there. Once the cells leave the bone marrow, the bone marrow need to reproduce themselves, then this process starts of hematopoiesis and there we can go back again to the concept of a balance. Of course, there is a certain beneficial physiological need of cell production, but one sees mechanisms so to say maybe go out of control and too many leukocytes are produced and released to the blood.                                            Then that again impairs patient outcome. There are very many papers, clinical papers, who have shown that leukocyte counts after myocardial infarction have a certain U shape relationship with the outcome. That I think is best described that if leukocyte counts are very high, that they actually negatively correlate with the outcome of MI patients. If you look at the bone marrow specifically, there are certain mechanisms, which we know, and what we are more closely looking at now, what are actually the modifier of this process, what are the signals which tell these cells to secrete more hematopoietic factors or quiescence factors? I think that's what also the Review is a little bit about. Cindy St. Hilaire:              Yeah, it's great. So, you were speaking about that kind of U-shaped curve in the release of these cells. Do we know based on some of the other things you spoke about, I guess I'm thinking about like diet or exercise or sleep in contributing to that release after an event like myocardial infarction. Is that known yet or has anyone looked into that? Matthias Nahrendorf:    Yeah. So, I think we're in the very beginning of understanding what's happening acutely. There's more knowledge on the chronic side and this is what we've been working on. Often the things that influenced the chronic situation can be quite different from what happens acutely. So I think in general, we're just beginning to understand what happens in acute myocardial infarction. Well, we know for instance is that exercise doesn't compromise the release and supply of leukocytes that's necessary in acute infection or acute myocardial infarction. So, if the mouse or the individual was exercising before the event, that may reduce overall leukocyte levels, but not to a degree that it's harmful. Cindy St. Hilaire:              Yeah. You can't exercise your way beyond a certain point. Matthias Nahrendorf:    Maybe that's also possible. If you run more than one marathon a day, I'm sure that's… Cindy St. Hilaire:              That will do something else. Matthias Nahrendorf:    Yeah. Cindy St. Hilaire:              Actually, so one of the interesting things that I saw in the article was when you were talking about diet and the role of diet in innate immunity, which is something I really never thought about, and you did bring up things like intermittent fasting. Can you discuss what's known at least scientifically about how that kind of diet timing can impact the immune system and therefore maybe cardiovascular disease? Matthias Nahrendorf:    So, that's a very emerging field. There's very little known about this. I think it's very interesting because very relevant and a lot of people are excited about it, but it's basically, from what I know, it's mostly two papers that were published, I think both in Cell, and they say that intermittent fasting leads to a decline of cells that are in circulation. So, that's a very exciting observation. I think it's similar insight as to discovering that immune cell levels circulate the circadian rhythms, which had been discovered a while ago. So, I think there's definitely an impact and we're just beginning to understand why this is and what regulates it. Cindy St. Hilaire:              Yeah, that segues nicely into the next thing I was wondering about and that is we all know not enough sleep, you get tired, your brain's not focused and stuff like that, but it really does impact the inflammatory system and also cardiovascular disease. So how is sleep involved in this innate immunity cardiovascular disease progression? Matthias Nahrendorf:    The way we approached this was actually thinking about lifestyle factors and their impact on cardiovascular disease. Maybe a decade ago, Fil, who's our middle author on this Review, and I started thinking about lifestyle factors and what struck us is that the association of some of these risk cardiovascular events is really high. So, if you look at sleep or if you look at psychosocial stress, psychosocial stress has an odds ratio of 2.4 for premature myocardial infarction. That is right on scale with all these powerful risk factors that everybody knows about like hypertension, but then what isn't really clear or maybe not entirely, is whether or not these risk factors also act via the innate immune system and that's where we were coming from.                                            I think at this point it's pretty clear that they do have an influence via the immune system. What I think what we've done is we uncovered a couple mechanisms that lead to the activation or dampening of inflammation depending on what you look at, but we don't really understand the broader network. I think there's a lot of work to be done looking into these pathways, which is exciting because I think that we can learn from nature what's dangerous and what's helpful. That this is how humans learn to fly. So, I think that observing what leads to cardiovascular disease, which behaviors are really harmful, will maybe lead us to new ways of mitigating it. Cindy St. Hilaire:              Yeah. Also, I think all of this, it's interesting. We all went after smoking for decades, stop smoking, reduce cardiovascular risk and maybe it's stress and sleep is the next smoking. Matthias Nahrendorf:    Smoking was so successful, right? I mean if you look 50 years back, it was promoted as this healthy thing that you should do. Then people really started to learn how bad it is and now we're at a time where smoking is declining and has declined and we see the results. Lung cancer is really on the decline. So, I think that's a good example how understanding health effects of behavior can be really helpful. Maximilian Schloss:        I think one thing I would like to add is when you ask more general question about innate immunity and when we talk about sleep and sleeping habits, I think what's generally quite interesting to know is that the immune system or these leukocyte numbers in circulation, they oscillate quite dramatically over the course of a day in a healthy human being and also in mouse models. I think one aspect also among others to consider is when we have unhealthy steeping habits, like for example, going to bed late or being a shift worker, drinking for example before going to bed. Then this will also confuse a system on the circadian entrainment, which then subsequently will lead to other problems.                                            I also think another thing is that what you were mentioning with the fasting is what we learned from this similar to these extreme circadian patterns seen when we fast or when a mouse is fasting, then monocyte levels drop into extreme low levels and these monocytes hone back into the bone marrow. I think this is interesting because it shows how dynamic actually a system like innate immune cells actually is. So, it's a very delicate system which responds to sleep disruption, exercise, diets in a very dramatic way. Cindy St. Hilaire:              All right, I'm going to bed early tonight and eating a good dinner. Well, this was a wonderful Review. I really enjoyed reading it. I really do think it's introducing the next targets that we have to go after in modifying cardiovascular disease. Thank you so much for taking the time to speak with me today. Matthias Nahrendorf:    Thank you. Maximilian Schloss:        Thank you so much. Cindy St. Hilaire:              That's it for our highlights from the March 27th and Compendium issue of Circulation Research. Thank you so much for listening. This podcast is produced by Rebecca McTavish, edited by Melissa Stoner, and supported by the editorial team of Circulation Research. Some of the copy text for highlighted articles was provided by Ruth Williams. Thank you to our guests, Max Schloss and Matthias Nahrendorf. I'm your host, Dr. Cindy St. Hilaire, and this is Discover CircRes, your on the go source for the most up-to-date and exciting discoveries in basic cardiovascular research.  

  On this week's episode, Stacy and Sarah are updating us about mushrooms! Since our last episode, Episode 307, we've discovered so much new information on mushrooms. Sarah considers them to be another food group! Find out why on Episode 392!   If you enjoy the show, please review it on iTunes! The Paleo View (TPV), Episode 392: Are Mushrooms Really Magic? Part 2 Introduction (0:44) Stacy isn't in charge this week! Time for Sarah to nerd out! Sarah is almost done with her gut microbiome book. She thinks only 2 months before she turns it in. Now that she has all this information on the microbiome, it's now of equal importance as nutrient density. "One of the foods that I have realized needs to be its own food group, needs to be emphasized, that just doesn't get enough play in any health conscious community is mushrooms." We did an episode on mushroom extracts in episode 307, but we only scratched the surface. Now we see mushrooms as a foundational food. We'll explore why in this episode. Stacy wants to see if we can figure out why she craves mushrooms with her steak when she has PMS Sponsored Episode by Real Mushrooms (8:48) Real Mushrooms is the premier provider of organic mushroom extracts, verified for the beneficial medicinal compounds like beta-glucans and free from starchy fillers like grains. With over 40 years of mushroom growing experience, Real Mushrooms prides itself on providing a transparent source of medicinal mushrooms that you can trust. Sarah has fallen in love with their super high quality, lab tested mushroom extracts as powder or pill or chocolate! Landing Page: https://www.realmushrooms.com/lp-thepaleoview/ Deal: 25% off, no coupon needed What mushrooms are their own food group (11:41) Not a vegetable! Fungus are a different kingdom from plants. Unique phytochemicals we can’t get anywhere else: polyphenols, triterpenes. Unique fiber we can’t get anywhere else: chitin, beta-glucans, chitosan Extremely nutrient dense Uniquely beneficial for the gut microbiome (mediates health benefits) A 100-gram serving of the least impressive mushroom (the white or common mushroom), raw, contains a whopping 24% of the RDA of vitamin B2, 18% of vitamin B3, 15% of vitamin B5, 16% of copper, 13% of selenium, 9% each of phosphorous and potassium, and smaller but still impressive amounts of vitamins B1, B6, B9, C and D as well as iron, magnesium, manganese and zinc—all for only 22 calories. While we don't count calories, that's certainly nutrient dense! Phytochemicals and fiber are very important for the gut microbiome. And then the gut microbiome breaks down nutrients for us to use. Phenolic compounds (17:50) All antioxidant, anti-inflammatory, and many other beneficial properties. protocatechuic acid. Studies suggest protocatechuic acid is a potent antioxidant that can reduce inflammation, protect the liver from damage, prevent cancer, protect against ulcers, and protect against cardiovascular disease, in addition to both anti-viral and anti-bacterial properties. gentisic acid. Studies suggest gentisic acid has anti-inflammatory, antirheumatic and antioxidant properties, can protect cells from damage caused by gamma radiation, can protect the liver from damage, and enhances antioxidant enzyme activity. gallic acid. Studies show that gallic acid has potent antioxidant effects, reduces inflammation, and may protect against cardiovascular disease, cancer, and infection. In fact, gallic acid may prove useful in the treatment of depression, cancer, and some types of infection. vanillic acid. Studies show that vanillic acid has antioxidant and anti-inflammatory properties and may even act as a pain reliever. It’s also cardioprotective, hepatoprotective, anti-fungal and anti-bacterial. p-coumaric acid. Studies suggest p-coumaric acid can reduce inflammation, reduce intestinal inflammation, regulate the immune system, improve bone density, act as an antidepressant, prevent cancer, protect against kidney damage, and protect against tissue damage caused by drugs and alcohol. Cinnamic acid. Another potent antioxidant, studies suggest that cinnamic acid has antibacterial, antiviral and antifungal properties in addition to protecting against cancer and diabetes. syringic acid. Studies show that syringic acid may protect against cancer, diabetes, liver damage and lung damage. myricetin. Studies show that myricetin is a superstar thanks to its strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities. It may protect against neurodegenerative diseases such as Parkinson’s and Alzheimer’s, as well as cardiovascular disease, liver damage, and glaucoma. Myricetin also protects against photoaging, thrombosis, hypertention, allergies and can even act as a pain reliever! catechin. Studies show that catechins act as antioxidants but also boost the activity of antioxidant enzymes. Catechins are also anti-inflammatory and modulate the immune system, anti-bacterial, anti-cancer and can boost metabolism and promote healthy weight loss. Catechin also helps shifting the gut microbiome towards a healthy microbiome from an obese microbiome. Present when they do a fecal transplant in mice. Triterpenes (26:37) Mushrooms are also particularly rich in triterpenes (including ergosterol, ganoleucoin, ganoderic acid and pyrrole alkaloids), which have a variety of properties that are important for cancer prevention, including antiproliferative, antimetastatic, and antiangiogenic. About 80 different triterpenes have been isolated from reishi alone, some of which are known to kill hepatoma cells (liver cancer cells), to inhibit histamine release from mast cells (anti-allergic effect), to have cardioprotective effects (by modulating angiotensin) and hepatoprotective activity. Fiber (29:28) Chitin Chitin is a type of fermentable oligosaccharide fiber made of long chains of a glucose derivative called N-acetylglucosamine with amino acids attached. It can only be obtained from mushrooms and other fungi, insect exoskeletons, fish scales, and shellfish shells. In studies, chitin has been shown to support the growth of species from Bifidobacterium (including Bifidobacterium animalis), Lactobacillus, Akkermansia, and Bacteroides while also decreasing the abundance of the inflammatory microbe Desulfovibrio. In mice, chitin oligosaccharides are also able to modulate the gut microbiota to combat diet-induced metabolic syndrome in mice, inhibiting the destruction of the gut barrier, restoring the Firmicutes to Bacteroidetes ratio to what it was before high-fat feeding, and reversing the decreases in Porphyromonadaceae, Deferribacteraceae, and Coriobacteriaceae and the increases in Rhodospirillaceae, Christensenellaceae, Bacteroidaceae, Lactobacillaceae, Bifidobacteriaceae, Verrucomicrobiaceae, and Erysipelotrichaceae induced by high-fat feeding. At the genus level, chitin fiber dramatically increased levels of Bifidobacterium, Lactobacillus, Akkermansia, and Bacteroides in these mice, while decreasing the abundance of the less favorable Desulfovibrio. In human fecal culture, chitin-glucan fiber also beneficially increases the Lactobacillus/Enterococcus ratio. Chitosan Chitosan is also composed of a long chain of N-acetylglucosamine molecules, but it also contains randomly distributed D-glucosamine molecules linked in a beta configuration. It is only naturally-occurring in the cell walls of fungi, like mushrooms. In mice, chitosan increases gut microbial diversity (along with a general increase in Bacteroidetes and a decrease in Firmicutes) and decreases levels of potentially pathogenic genera Escherichia and Shigella. In diabetic mice, chitosan has also been shown to reshape the microbiota to induce an anti-diabetic effect, relieving dysbiosis by raising levels of Akkermansia muciniphilia and suppressing the growth of Helicobacter. Beta-Glucans Glucans are polysaccharides derived from D-glucose, linked by either alpha-glycosidic bonds (making them alpha-glucans) or beta-glycosidic bonds (making them beta-glucans). Mushrooms are particularly rich sources of beta-glucans (more specifically (1-3),(1-6)-beta-glucans which are different than the (1,4)-beta-glucans in grains like oats), which feed anaerobic microbes in the gut and can significantly increase levels of, butyric and propionic acids (the second best source of beta-glucans is oats). Beta-glucans have been shown to increase levels of Roseburia, Bifidobacterium and Dialister, and in particular the species Eubacterium rectale, Roseburia faecis, and Roseburia intestinalis. In a human trial, foods rich in beta-glucan, increased levels of Roseburia hominis, Clostridiaceae (Clostridium orbiscindens and probiotic Clostridium species), and Ruminococcus species, while lowering the levels of Firmicutes and Fusobacteria were lowered. Levels of acetic, butyric, and propionic acids also increased. In vitro studies have also demonstrated that beta-glucan can boost the growth of Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium animalis lactis. In an extensive review of the health effects of beta-glucan, researchers concluded that this fiber’s actions upon the gut microflora, including enhancing the production of short-chain fatty acids, contributes to its anti-cancer, anti-inflammatory, anti-diabetic, and immune-modulating effects. FAQs (37:44) Taken all together, these unique properties found in no other food groups elevates mushrooms to their own food group! Serving size? Servings per week? Let’s look at the science! Servings are defined same way as veggies, 80-100g, one cup raw (a fist-sized amount) or 1/2 cup cooked. Cancer studies show highest magnitude of effect in relation to frequent mushrooms consumption. Many (but not all) CVD and T2D studies show null effect in context of SAD diet. https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.32591 Compared to participants with mushroom consumption

Join the EMGuideWire Crew from CMC EM Residency Program as they discuss Ludwig's Angina and the management Priorities!!! BACKGROUND Angina = “Strangling” Bilateral infection of submental, submandibular, and sublingual spaces 70-85% of cases arise from odontogenic source Periapical abscesses of mandibular molars Piercings (frenulum) URI more common cause in children Source of infection often polymicrobial Most commonly viridans; also Staphylococcus and Bacteroides species Patients usually 20-60 years-old; more common in males1 Mortality in treated Ludwig’s Angina = 8%7 ***Airway compromise = leading cause of death8 Who Is At Risk? Diabetes mellitus Chronic alcohol abuse IVDA HIV/AIDS Malnutrition Poor oral hygiene Smokers Anatomy & Pathophysiology Mylohyoid subdivides submandibular space: Sublingual space Submaxillary (submylohyoid) space Infection extends posteriorly and superiorly, elevating tongue against hypopharynx If left untreated, can extend inferiorly to retropharyngeal space and into superior mediastinum3 Clinical Signs & Symptoms Dysphagia Odynophagia Trismus Edema of upper midline neck and floor of mouth Raised tongue "Woody" or brawny texture to floor of mouth with visible swelling and erythema Late Findings Drooling Tongue protrusion Trismus Dysphonia Cyanosis Acute laryngospasm Stridor Patients may demonstrate signs of systemic toxicity → fever, tachycardia, and hypotension How Do I Make the Diagnosis? Clinically! Consider CT head/neck Can help evaluate extent of infection if clinical situation persists CBC Chemistry Lactate Blood Cultures Management Emergent ENT/OMFS consult for I&D in OR and extraction of dentition if source is dental abscess Airway Management Intubation will be VERY difficult due to trismus and posterior pharyngeal extension Ideal situation = awake fiberoptic intubation in OR ALWAYS have a surgical airway ready as your back up plan Blind insertion devices (e.g. intubating LMA) are NOT recommended Management - Antibiotics Must cover typical polymicrobial oral flora Immunocompetent 3rd-generation Cephalosporin + (Clindamycin or Metronidazole) Ampicillin/Sulbactam Penicillin G + Metronidazole Clindamycin (allergic to penicillin) Immunocompromised → *Need MRSA and GNR coverage!3 Cefepime + Metronidazole Meropenem Piperacillin-tazobactam Add Vancomycin if concern for MRSA risk factors Steroids Dexamethasone 10 mg IV Thought to chemically decompress for airway protection and increase antibiotic penetration6 Nebulized epinephrine Resuscitation and pain control Complications Intracranial infections (e.g. CST, brain abscess) IJ thrombophlebitis (Lemirre’s Syndrome) Mediastinitis Mandibular osteomyelitis Empyema Pearls Three characteristics of Ludwig’s angina can be remembered as the 3 Fs: Feared Often Fatal Rarely Fluctuant ABCs—Sit upright Early notification of ENT/OMFS and anesthesia to facilitate definitive airway management Arrange for the patient to be admitted to ICU Priorities!!! Secure the airway EARLY! Prepare and be ready for a difficult airway — expect that the patient will require a surgical airway Prevent the development of septic shock and multi-organ failure — give antibiotics early References Lin HW, O’Neil A, Cunningham MJ. Ludwig’s Angina in the Pediatric Population. Clin Pediatr (Phila) 2009;48:583-7. Baez-Pravia, Orville V. et al. “Should We Consider IgG Hypogammaglobulinemia a Risk Factor for Severe Complications of Ludwig Angina?: A Case Report and Review of the Literature.” Medicine. 2017;96(47):e8708. Pandey M, Kaur M, Sanwal M, Jain A, Sinha SK. Ludwig’s Angina in children anesthesiologist’s nightmare: Case series and review of literature. J Anaesthesiol Clin Pharmacol. 2017 Jul-Sep;33(3):406-409. Botha A, Jacobs F, Postma C. Retrospective analysis of etiology and comorbid diseases associated with Ludwig’s Angina Ann Maxillofac Surg. 2015 Jul-Dec;5(2):168-73. Parhiscar A, Har-El G. Deep neck abscess: a retrospective review of 210 cases. Ann Otol Rhinol Laryngol 110: 1051, 2001. Saifeldeen K, R Evans. Ludwig’s Angina. Emerg Med J 2004; 21: 242-243 Nanda N, Zalzal HG, Borah Gl. Negative-Pressure Wound Therapy for Ludwig’s Angina: A Case Series.Plast Reconstr Surg Glob Open2017 Nov 7;5(11):e1561. Pak S, Cha D, Meyer C, Dee C, Fershko A.Ludwig’s Angina. Cureus. 2017 Aug 21;9(8):e1588.  

There appear to be just two types of people in the world: those who have mostly Bacteroides type bacteria in their gut, and those whose colons are overwhelmingly home to Prevotella species instead.

Food Scientist, Kriben Govender (Honours Degree in Food Science & Technology) and James Shadrach (Honours Degree in Psychology) have a wide-ranging discussion with Citizen Scientist Keith Bell on Microbiome stool testing, strategies to modulate gut bacterial composition for optimal health, epilepsy, gut-brain axis, rain forming bacteria, the importance of viruses, gut centric remedies for anxiety and depression, microbiota - mitochondria interaction, kefir and much more   Bio:    Keith Bell is a citizen scientist particularly interested in gut-brain connection including the gut origin of seizure, underdiagnosed in epilepsy. Published articles include topics such as microbial predisposition, fetal colonization, microbe translocation and vaccine safety. He's founder of Sanitation Circle and 25 year veteran of the recycling industry with interest in sanitation and health. During the 1980s, he was a UNICEF radio spokesperson in Chicago for the annual release of State of the World's Children Report. He believes "Sanitation is Sanity" and that microbial balance is an internal and external environmental issue of the highest order. Keith founded The Gut Club in 2016 to create awareness about the importance of intestinal health to general health and provide support for treatment and prevention of metabolic disease.   Topics discussed:   The Glut Club - the hub of microbiome citizen science Analysis of stool test results Microbiome differences across the world Geography, diet and microbiome diversity Allele Microbiome Stool testing Obesity- Firmicutes and Bacteroidetes The immune response guidance by microbes The function of Peyer’s Patches Vaccine response in high Bacteroides cohort Obesity and Lipopolysaccharides (LPS) Persia the Cradle of Bacteroides Prevotella- Fibre eater Microbiome changes after migration Consequences of a shift from Prevotella to Bacteroides The Gut - Could it be the Environmental Issue of our time The Gut and Epilepsy  Rain Making Bacteria and Fungi (see laboratory experiment) https://youtu.be/SenJud3cHLc CO2 sequestering by microbes Exchange breathing method for seizures Diets for Epilepsy Forum The impact of Metformin on the microbiome Bacteriophages (viruses) and early infancy immunity The River Ganges - bacteriophages Personalised medicine via stool test charts Shifting the gut microbiome Autoimmune and Bacteroides dominance Keto, Paleo, Low carb and Carnivore Diet benefits and flora shift The Microbiome and Mental Health Kriben’s struggle with anxiety and depression Environmental factors that cause depression The Gut-Brain Axis The Impact of Stress on Bifidobacteria and Lactobacilli Lactobacilli, Oxytocin and empathy Oxytocin, autism, eye contact and touch Clostridium, serotonin and tryptophan metabolism Amino Acids neurotransmitter balance and microbes Serotonin Syndrome SSRIs Gut, Brain and Heart connection GAPS Diets- Natasha Campbell McBride Kefir Fermentation time and Lactobacillus domination  Fibre, Butyrate production, oxygen, microbiome modulation The importance of the mucous layer Acacia, Partially Hydrogen Guar Gum- Prebiotics Inulin and bloating Fasting and Microbiome Composition Gut Club Stool Testing Discussion Group https://www.facebook.com/groups/TheGutClubStoolTestDiscussionGroup/ The citizen science of sharing microbiome stool charts Autism and Stool test results Faecal Microbiome Transplants Probiotic enemas Breastfed baby poop- untapped medicine Infant stool History in China Bacteroides dominance The impact of excess Bifidobacteria and Akkermansia Race, Gender and Geography of Microbiome Diversity Microbiome and Mitochondrion interaction The impact of antibiotics on mitochondria and ROS production Keith’s top gut health tip Microbial modulation of Vitamin D Dr Jack Kruse interview - Light and the Microbiome https://podcast.nourishmeorganics.com.au/dr-jack-kruse-on-light-and-the-microbiome Brought to you by:   Nourishme Organics The Gut Health Superstore   Shop Gut Health here:   https://www.nourishmeorganics.com.au/   Use code guthealthgurus for 10% off        Allele Microbiome- Australian Provider of World Leading Metagenomic Whole Genome Stool Testing   Learn more about Metagenomic DNA based Stool Testing:   https://www.allele.com.au/collections/frontpage/products/gut-microbiome-analysis       Connect with Keith Bell   Website- https://thegutclub.org/       Connect with Kriben Govender:    Facebook- https://www.facebook.com/kribengee/ Instagram- https://www.instagram.com/kribengovender/ Youtube- https://www.youtube.com/c/Nourishmeorganics?sub_confirmation=1 Gut Health Gurus Facebook Group: https://www.facebook.com/groups/nourishmeorganics/ Mito Wellness Support Facebook Group: https://www.facebook.com/groups/347845406055631/   Download links                 If you enjoyed this episode and would like to show your support:   1) Please subscribe on Itunes and leave a positive review     Instructions:   - Click this link  https://itunes.apple.com/au/podcast/gut-health-gurus-podcast/id1433882512?mt=2   - Click "View in Itunes" button on the left-hand side - This will open the Itunes app - Click the "Subscribe" button - Click on "Ratings and Reviews" tab - Click on "Write a Review" button   Non-Itunes users can leave a Google Review here: https://goo.gl/9aNP0V     2) Subscribe, like and leave a positive comment on Youtube   https://www.youtube.com/c/Nourishmeorganics?sub_confirmation=1   3) Share your favourite episode on Facebook, Instagram, and Stories 4) Let your friends and family know about this Podcast by email, text, messenger etc   5) Support us on Patreon for as little as $5 per month and get same day, early access to our latest podcasts (typically around 4 to 6 weeks earlier than the general public) https://www.patreon.com/nourishmeorganics     Thank you so much for your support. It means the world to us.

For this episode, join Josh Herskovitz and Emma Farquharson as these two "twins" from the Goddard and Nugen Labs use their "sibling humor" to summarize some of the most recent and fascinating literature in Food Microbiology.This month, for our 10th episode (but 1st episode of Season 2), our speakers walk us through two new papers, while also splendidly enunciating the ways in which these findings connect to what currently is practiced within the field of Food Microbiology. Josh and Emma examine how the low levels of persistent glucose and fructose in Western diets directly interfere with the colonization of Bacteroides thetaiotamicron - a critical organism for good health. Next, these two friends chat about the use of pectins as a colonization aide prebiotic, instead of the classical concept of prebiotics as fuel for cells!We eat food every day, so it makes sense that it would be a consistently hot topic of research. So join us this month as we explore how foods can hurt AND help our health.[[If you have a moment, be sure to rate us 5 stars. It might seem silly, but those ratings help our group to get more attention and to spread new literature to those of us too busy to sit down and comb through the primary literature. If you have any questions or comments, or if you have a suggestion on how we might make our podcast even better - feel free to leave a comment with your thoughts or email us at "foodmicrominutes@gmail.com".]] Here at F.M.M., we believe in open communication as a way of highlighting the massive benefits of collaboration between scientists. Thanks for listening!

Was hat der Darm mit Abnehmen zu tun? Mehr als man glaubt! Es gibt immer mehr Experten und Studien die einen Zusammenhang zwischen Darmbakterien und Gewicht zeigen. Wenn das Verhältnis zwischen Firmicuten und Bacteroides nicht mehr stimmt kann das zu Übergewicht führen. Ich starte nun meinen eignen Test und mein persönliches Darm Diät Projekt Du kannst mir dabei Folgen auf YouTube, Instagram oder Facebook. Hier die Bücher aus der Folge: Die Darm-Diät von Anita Frauwallner No Carbs: Das Kochbuch zur Darm-Diät von Anita Frauwallner  Schlank mit Darm von Michaela Axt-Gadermann          Das Darm-Schlank-Programm von Mathias Oldhaver & Pia-Franziska   Du willst mehr zu der Darm Diät wissen? Schreib mir unter E-MAIL: darmdiaet@ask4more.at Folge mir auch auf folgenden Kanälen: ► Instagram: https://www.instagram.com/darmdiaet ► Facebook: https://www.facebook.com/darmdiaet/ Gruppe Die Darm Diät / http://bit.ly/DarmDiät_FBG ► Blog: http://ask4more.blog/ Newsletter: http://www.ask4more.at/darm-diät/   Und vergiss nicht: Sei auch du die beste Version die du sein kannst, unter Nutzung deines vollen Energiepotentials! Teile diese Folge mit Personen die dir wichtig sind. Ich freue mich darauf!

Today, we are talking about gut bacteria and it's relation to chronic fatigue, I.B.S., and acid reflux. We are also going to cover the types of food to eat, the ones to stay away from, and how to properly consume them to help us with our body's absorption and digestion. And my favorite - He is going to share why our mothers and grandmothers have been right the whole time. Eat Slow and Chew Well. Norman Robillard, Ph.D., Founder of Digestive Health Institute is a gut health expert, author and microbiologist. He is the creator of Fast Tract Diet – Fermentation Potential (FP) System, author of the Fast Tract Digestion book series and publisher of the Fast Tract Diet mobile app. Dr. Norm received his Ph.D. in microbiology from the University of Massachusetts, Amherst studying Bacillus anthracis and other Bacillus species. His post-doctoral training at Tufts University, Boston focused on antibiotic resistance gene transfer. He was the first to demonstrate the transfer of genes (via conjugation) between the anaerobic gut microbes Bacteroides fragilis and E. coli.

Thank you for joining us for our 2nd Cabral HouseCall of the weekend! I’m looking forward to sharing with you some of our community’s questions that have come in over the past few weeks… Let’s get started!  Anonymous: I am curious about your thoughts on iron levels. I don’t recall hearing you ever talk about it on the podcast. A few months ago I thought I had mono - I had all the classic symptoms. Though I didn’t check my blood work I started taking iron and felt much better. My doctor said I was most likely anemic as I was a vegetarian at the time. What are your thoughts on iron levels as it relates to mood, energy etc? Vivian; After listening to your podcast on signs that a disease is coming , i got really concerned cause my husband showed one , very clearly - the diagonal crease on ear lob - His mom passed in 2010 at age of 60 , suddenly from heart disease they never knew she had. After that , in 2011 , he did a full scan and all showed fine. I told him about the podcast and forced him to do it over....we just got a call from the doctor , saying that he has the early stage of a heart disease...that one one of the markers that in 2011 came as zero, came as a 4 now and his red blood cells are kind of "sticky" and can result in heart problems if he doesn't eat right and follow the recommendations. Since i met him , over 2 years ago, his diet has changed completely, i thought him how to eat and all i have learned about nutrition. He finished a doctor Cabral 7 days detox couple weeks ago. Please , what are your recommendations ( what to avoid and what to supplement with) so we can do our best to have him with us for many ,many, years?? I appreciate your help and all you do. Suzanne:  Hello Stephen! Thank you for all the wonderful work you do in the healing world! My question involves a few different sicknesses I’ve accumulated over the last year. Last year during a stressful teaching stint I was diagnosed with an Epstein Bar (Glandular Fever) relapse, despite having the condition in my late teenage years. (I am now 25 years old.I suffered with a chronic sore throat initially which turned into fatigue, muscle aches and peeling fingers and toes. After changing a huge amount of my lifestyle and stress I have helped things but still suffer from the sore throat every few days, fatigue and constant peeling of my fingers and toes. (Despite many coconut oil applications I can’t seem to stop the peeling) On a side note: I have travelled a lot (and did get bitten by a tick in Nepal.) I have been on far too many antibiotics (If only I knew) and did go on a course of Roaccutane for three months. I was also vegan for almost four years in an attempt for perfect health which has since changed since the long absence of my period. My sickness also began when I was vegan. I now eat a small amount of meat including salmon, organic chicken and kangaroo which has fixed my hormones. (Still no dairy, eggs and limited gluten.) BUT Despite my best efforts I’m still fatigued and working part time as a result with peeling fingers and a sore throat most of the time) I believe I will get there I just need a little help and advice. Thank you for all the work you do in this field. The path to wellness in the best gift you could give. Elizabeth: Hi Dr Cabral, I don't think you have done a podcast on this but I was wondering if there is anything you would specifically recommend for PMLE? I have read online that Shirudo AGR+E lotion is good but I wondered if there is also anything else or any supplements that would help (and/or potentially reverse) this? It may help to mention, I believe I have hypothyroidism (which I am naturally treating the past year or so) and that I have changed my sunscreen various times (minor PMLE occurs with each different sunscreen brand; I am also trying to find a natural sunscreen). The PMLE type reaction is relatively minor and has only started to happen the last couple of years. Last summer vacation I had a minor reaction on my arms, legs/ankles and chest and this vacation this past week (mid-June) I had it only on my hands, knees, feet and partly on my collarbone/upper chest. It's not immediate, it seems to take a few days to occur. I remain out of the sun when it does, although using more sunscreen does not help. Not sure if reaction on different areas of the body signifies anything? I am from London, where we don't get much sun. Perhaps there is a relation with thyroid but it would be useful to know what may help it going forward and what may have caused it. I am going away again soon so I did contact your support email in hope for a earlier response but they directed me to ask cabral, however hopefully this may help some others... Thank you so much for you and your podcasts! Andrea: My 25 yr old daughter has had gut issues for years and has been to many dr,’s but still no relief. She was then diagnosed with Hashimotos and thyroid cancer and had her thyroid removed 12/2016. She now also has psoriasis. She now see’s a local Functional medicine dr here in STL who has been trying to help her. She tried a candida cleanse late last year but still has gut pain. She is gluten free and has done food allergy tests that show mild allergy to yogurt but that’s it. She decided to do a GI Map and here are the things that seem off:Enterotoxigenic E. coli LT/ST 1.19e6 High; Normal Bacterial Flora; Bacteroides fragilis 8.8e8 Low; Bifidobacterium spp. 1.6e10; Enterococcus spp. 5.7e6; Escherichia spp. 7.9e5 Low; Lactobacillus spp. 2.6e6; Clostridium spp. 9.66e4; Enterobacter spp. 1.69e5 Low; Phyla Microbiota Result; Bacteroidetes 1.94e10 Low; Firmicutes 7.87e9 Low; Firmicutes:Bacteroidetes Ratio 0.40; Additional Dysbiotic/Overgrowth Bacteria Result Normal; Bacillus spp. 2.71e4; Enterococcus faecalis

Today’s show explores your microbiomes, the different biomes between breast cancer and healthy breasts, and even how pollution can attack these microbes. You’ll also learn how Pollution Attacks Your Biomes and what you can do about it.  Inside the human body are nooks and crannies, called biomes, teeming with microbial life that includes viruses, bacteria and fungi.  We have “biomes” throughout our entire body. We have biomes in our eyes (the ocular biome), mouth (oral biome), in our esophagus, stomach, small intestine, colon (most commonly thought of as our microbiome), in our tonsils, vagina, respiratory tract and lungs, in the uterus, urethra, prostate, skin, and even inside our brain. There are biomes deep inside the chambers of your heart. Your colon is your most biome dense organ. It’s the most studied so far. But in today’s radio show you learn about your many biomes, especially inside the breast! Biomes give off peptide signaling molecules that allow biomes to cross-talk with each other and also with distant tissues like your brain. Biome signals and cross-talks are how biomes enormously influence our state of wellness or illness. Biomes are so powerful they are now being referred to as our “third brain.” First brain—in your head Second brain—enteric nervous system inside your gut Third brain—sum total of microbial life inside all your biomes We inherited healthy ancestral microbiomesfrom long ago. But with today’s lifestyle, including the Standard American Diet (SAD) and toxic exposures from the environment, these healthy protective microbes are getting “ill” and making us ill. There are “disease signature dysbiotic” conditions. This means there are distinctive microbial fingerprints for various diseases. For example, patients with multiple sclerosis will have common dysbiotic microbial patterns. So will bulimic patients. So will breast cancer patients, inside their breast tissue! So do Crohn’s inflammatory bowel disease patients. So do post-bariatric surgery patients. And kidney stone formers. And even for Alzheimer, Parkinson, diabetes, and heart disease sufferers. The list goes on and continues to grow. Diet is the most powerful driving force for the health of these biomes. Hormone-altering chemicals from your personal care products, or from plastic containers you wash in the dishwasher and use for food, or from sitting in polluted traffic, can all adversely affect your precious biomes. Cleveland Clinic researchers discovered that breast cancer patients have different breast biomes than breast tissue without disease. “Healthy” breast tissue, from women who didn’t have breast cancer, contains more of a healthy bacterial species called Methylobacterium. Women with breast cancer had much less, if any, Methylobacterium. Different types of breast cancer have different symbiotic signatures. ER positive and Her2 positive shared a microbiotic signature, while triple negative and triple positive shared a similar microbial pattern. A lactating breast has a microbiota based on what the mother eats, the bugs on her skin and her gut, and the pollutants she’s been exposed to throughout her life. In contrast to vaginally delivered infants, the gut microbiotaof infants delivered by C-section are significantly less similar to their mothers. Cessation of breast-feeding, rather than introduction of solid food, is what turns a baby’s microbiome into an adult-like microbiota. At three years old, a child’s microbiome starts to look like an adult. How a baby is delivered initiates the health of their microbiota (the sum of all their biomes). A new born moving through a healthy vaginal biome gets a healthy start. Obese junk-food eating moms will have less healthy vaginal biomes and babies will get a less healthy start. Breastmilk’s microbiota takes it from there, and continues to influence the health of the newborn’s microbiota. Breast milk stimulates healthy organisms in the infant’s gut like Bifidobacteria, Lactobacillus, and Bacteroides. Short-chain fatty acids in breastmilk activate receptors on T-reg cells and specific genes, so the baby won’t have leaky gut or gut inflammation. Other components of breastmilk (defensins, lactoferrin, etc.) inhibit pathogens and further contribute to microbiota composition. Healthy breastmilk and the vaginal microbiome stimulate baby’s intestinal microbiota to prevent asthma, inflammatory bowel disease, type 1 diabetes and even illnesses when the baby grows up. The World Health Organization published that polluted air, with excess particulate toxins, is a major contributor to diverse diseases from diabetes to cancer to dementia. Hold on to your hats, air pollution is also being linked to “biome damage.” You’ll hear more about all this on today’s power packed show.  

90% of your microbiome is made up of two phylum’s, the Firmicutes, and the Bacteroides. There is a lot of research going into these two bacteria because the more we learn about gut health, the more links there are to obesity and disease epidemics --- check out this weeks podcast as we chat a bit more about these two bugs and how they work.

In our newest podcast, we talk about autoimmune diseases linked to the Kissing Disease, concerns over the emerging Nipah Virus, and how fetal immunity may be causing babies to be born early. Topics Epstein-Barr Virus and Autoimmunity (2:20-12:00) Nipah Virus Outbreaks (12:01-20:35) Bacteria Coats itself with IgA for Protection (23:23-32:23) Out of Whack Fetal Immune Systems Prompt Preterm Labor (35:45-43:33) Keywords: autoimmunity, kissing disease, mononucleosis, Nipah Virus, herpes, Epstein-barr virus, cancer, bats, reservoir, Bacteroides fragilis, IgA, gut, mucosa, bacteria, pregnancy, premature birth, fetal immunity, preterm  

Pre and Probiotic Use in SIBO In this episode, Dr Nirala Jacobi is in conversation with Dr Jason Hawrelak on the topic of all things gut. Dr Hawrelak is a researcher, lecturer, naturopath, and nutritionist with over 16 years of clinical experience.  He also practices at Gould's Natural Medicine - a 135 year old natural medicine apothecary and clinic in Hobart, Tasmania, Australia.   Dr Hawrelak completed his PhD examining the capacity of probiotics, prebiotics, and herbal medicines to modify the gastrointestinal tract microbiota.  He is currently the senior lecturer in Complementary and Alternative Medicines at the University of Tasmania's School of Medicine where he coordinates the evidence based complementary medicines programs.  Dr Hawrelak also teaches the gastrointestinal imbalances unit, within the Masters of Science and Human Nutrition, and Functional Medicine Program at the University of Western States, in Portland, Oregon.   Topics discussed in this episode include: Dr Hawrelak's 2016 lecture on Pre and Probiotics at the SIBO Summit 2017 - still available to practitioners as part of the SIBO Fundamentals online course. The website Dr Hawrelak developed, Probiotic Advisor, to help practitioners differentiate which probiotic strains and products are appropriate to different conditions. Recent probiotic research (2017) in relation to SIBO treatment and methane reduction. The importance of strain specificity in relation to therapeutic effect. Reseeding the gut with exogenous probiotics as an outdated concept, and the history of this ideology. Faecal transplants and the capacity of strains to remain in the gut as compared to probiotics taken in capsule form that does not. What metabolic modulation actions do probiotics have in the body, and how to integrate this with background changes to enhance the therapeutic effect. D-lactate V.S. L-lactate producing probiotic strains, and what systemic effects do each trigger? D-lactic acidosis and when this may occur. SIBO related symptom presentation and strain specificity for probiotic therapy, for symptoms such as motility issues, abdominal hypersensitivity, histamine issues, food reactions.   Motility Probiomax for motility Bifidobacterium Lactis HNO19 - 1-2 capsules per day. BB12 Bifidobacterium Lactis for motility. Suggestions on the combination use in children with constipation. Animal study showing probiotic strains that work on the migrating motor complex function - prokinetic potential. Combination of L. Rhamnosus GG, Bifidobacterium BB12, and inulin.   Abdominal hypersensitivity in SIBO Bifidobacterium Infantis 35624 Align Rhamnosus GG Functional abdominal pain in kids - meta analysis supporting this therapeutic application. Nissle 1917 strain of E.Coli Bifidobacterium Lactis DN173010 Speed up transit time Decrease pain and bloating Yoghurt brand, Activia, available in US, is the only available form (as currently known)   Leaky Gut Probiotics useful in helping to repair leaky gut Rhamnosus LGG Biocodex preparation of Saccharomyces Cerevisiae/Boulardii   Histamine Intolerance Infiltration of mast cells into the intestinal wall in SIBO and histamine implication. Probiotics and histamine degradation - investigating Rhamnosus Infantis Plantarum Probiotics and histamine upregulation - investigating Casei Bulgaricus High-fat diets producing many bile salts, which feed hydrogen sulfide producing bacteria, and hydrogen sulfide gas contributing to leaky gut. Higher fat diets contributing to diamine oxidase (DAO) enzyme overuse in the small intestine and why this is relevant to histamine. Ketogenic diets and symptom resolution - why is this, and is it sustainable? The impact of starving out butyrate producing colonic flora. The risk of ketogenic diets.   Continued How to reintroduce foods to sensitive patients Heal gut Decrease inflammation Work on allergy axis to increase dietary diversity Partially hydrolysed guar gum (PHGG) as a prebiotic Probiotics as aiding in the recovery of the microbiome after an insult, eg chemotherapy, antibiotics, radiotherapy etc. Prebiotics and changes of diet having a greater impact on the gut microbiome. Jason's prebiotic use PHGG - use in functional constipation patients, non-methane type SIBO, and diarrhoea type stool conditions. Helps to normalise stool. Bimuno - galacto oligosaccharides Bringing bifidobacterium, and faecalibacterium prausnitzii populations back. Faecalibacterium prausnitzii: The single species with the highest prevalence in healthy people. Predominant butyrate producer. Produces another anti-inflammatory gut healing compound, so helpful for inflammatory bowel diseases. Higher levels as protective against metabolic syndrome and Type 2 Diabetes. Akkermansia Accounts for 1-3% of the microbiome in healthy people. Eats mucin, therefore if inflamed guts producing a lot of mucus can overgrow akkermansia. Lactulose Use as a prebiotic. Increases faecalibacterium prausnitzii, akkermansia, and bifidobacteria, lactobacilli. Use as a pH changer - moves environment to be more beneficially acidic. Amazing capacity to decrease Bacteroides numbers - which can increase after multiple courses of antibiotics. SIBO positive on Lactulose breath test patients - to attend to SIBO with therapy first before using Lactulose as a prebiotic. Lactulose uses in recurrent urinary tract infections as supported by clinical trials - as it decreases levels of E.coli in the gut so fewer pathogens can make the journey from the anus, to the vagina, to the urethra. Prokinetic for small intestine and when it is appropriate to use it in SIBO. Note: lactulose will increase gas, but not bloating. If bloating, cease use. Discussion on soil based organisms as they relate to functional digestive disorders.   Resources BioGaia sunflower oil based probiotics Blackmores Digestive Bio Balance Rob Knight - microbiome specialist Products mentioned: Motility Probiomax Bifidobacterium Lactis HNO19 - 1-2 capsules per day. Lactobacillus reuteri MM53 BioGaia strain Testing mentioned Ubiome GI effects from Genova Diagnostics Dr Hawrelak's Probiotic Advisor    

[intro music]   Hello, and welcome to Episode Thirty-One of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Dr. Lloyd Kasper about the gut microbiome and its role in MS. But to begin, here is a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org.   Last week our parent organization, the Accelerated Cure Project, launched its latest endeavor called “iConquerMS.” iConquerMS aims to enroll 20,000 people living with MS to play an active role in research, empowering them to securely submit their health data, influence the studies that are carried out by the initiative, and stay informed about the research. Visit iConquerMS.org for more information.   Vision and sensorimotor problems go together in some MS patients. A recent publication in the journal Neurology examined the relationship between MRI measures of the spinal cord and retina in patients with MS. The investigators found some correlation between the two types of metrics, but they also found that damage in each structure had independent relationships with disability. Read the full story in our “news and future directions” section.   And lastly, our previous podcast contained an error. We mentioned a story about a proof-of-concept study of a novel way to monitor lesion repair. However, the story was withheld from publication due to a delay in the release of the research article. The story is now live on our website.   [transition music]   Now to the interview. Dr. Lloyd Kasper is a faculty member of the Geisel School of Medicine at Dartmouth College. He met with MSDF Executive Editor, Bob Finn, to talk about his research on the gut microbiome and MS.   Interviewer – Robert Finn Dr. Kasper, welcome.   Interviewee – Lloyd Kasper Thank you.   MSDF So to start, why on earth would someone interested in a neurological disease such as MS concern himself with bacteria in the intestines; what’s the connection?   Dr. Kasper That’s actually a very valid question. And the answer to that question is pretty straightforward, is that there’s a very clear brain-gut access so that the brain talks to the gut primary modulating the physiology of the gut through secretion of a variety of molecules, vasoactive proteins, etc. That in turn affects the motility of the gut. By affecting the motility of the gut, you also affect everything that’s inside the gut, which is – as you mentioned just previously – the 100 trillion bacteria that each and every one of us in this world has. And those bacteria in response to the changes in motility shift their behavior, because these are living organisms, and they secrete a wide range of metabolites.   For the purposes of simplicity, you can look at those metabolites and the effect of those various metabolites on the immune system, taking into account that the gut is the largest immune system in our body – 80% of our immune cells are in the gut. So you’ll have this clear interaction between the brain, its activity physiologically on the gut, and the gut’s activity on the bacteria, and then the bacteria’s activity back on the immune system which leads to issues related to the brain.   MSDF So you partly answered my next question. There are microbiomes in other places besides the gut – the skin, the urinogenital tract, etc. Do those other microbiomes have any affect or any relationship to multiple sclerosis, do you think?   Dr. Kasper First of all, the association between the gut microbiome and MS has not yet been fully established, there’s experimental data that would suggest that there is a relationship between the two but that’s still at the experimental level. There really has been very little exploration of the other microbiomes within the body. Remember, the microbiome is not just the microflora. What the microbiome is is the genome of the flora in its relationship to the genome of its host. So when you look at the genomics of MS, for example, in the host – which there’s a lot of work that’s being done – you’re only looking at a fraction of the genetic material that’s involved in this relationship between the gut and the body that it’s in OR any of the other sites that we have microflora – our mouth, as you pointed out; our ears – inside of our ears; our lungs. Those are all areas that bacteria in our body exists in balance with us to achieve a homeostasis. The reason for looking at the gut microbiome is that because it’s the largest, probably the most complex as well.   MSDF So you focused much of your attention on a single bacterial species. Let me see if I pronounce this correctly – Bacteroides fragilis– am I close?   Dr. Kasper Correct.   MSDF And a single substance that it produces, polysaccharide A, or PSA – which has no relation to prostate specific antigen. Why are you focusing on that species and that product?   Dr. Kasper Well, there is mounting evidence that there are several phyla that colonize the gut. The two major phyla of interest are Firmicutes, which are gram-positive aerobes, and Bacteroides, which are gram-negative anaerobes. I’m talking about at the phyla level over which there is no kingdom, phylum, class, order, family, genus, species. Under each one of those phyla there are many different species. We’ve focused in on primarily Bacteroides because Bacteroides fragilis is a very common commensal that essentially inhabits in the neighborhood of 80-90% of all mankind in the world. Bacteroides as a phyla has been associated with the induction of regulatory T cells. Regulatory T cells live in the colon, in and around the colon, and that’s where Bacteroides live. And it’s been shown that Bacteroides as a phyla have the capacity to drive regulatory T cells.   The reason it’s important in MS is because there is a known deficit in the regulatory T cell population in patients with MS. And we chose Bacteroides fragilis because of all the Bacteroides species, that’s the one that we actually know most about immunologically. There’s at least 20 or 25 years’ worth of very, very important data that shows how this particular molecule, this polysaccharide A – and it’s a polysaccharide, it’s not a peptide, it’s a polysaccharide – how this polysaccharide can drive the immune system to a regulatory phenotype that’s associated with the induction of regulatory T cells, production of IL10, all those factors which are important in MS which we know are deficient in those with MS.   MSDF When you say drive the immune system, drive T regs, what do you mean by that?   Dr. Kasper Basically, these bacteria have the capacity to convert effector cells, which would be CD4 positive CD25 negative cells to a regulatory phenotype, which would be CD4 CD25 positive associated with sort of the standard-bearer of regulatory cells, which is Foxp3, which is a nuclear antigen that’s been characterized with it. So this molecule has a remarkable capacity to do that both in vivo and our studies show you can do that actually in vitro as well. So you can take cells that are negative that would be considered naïve or effector-type cells, culture them with this PSA molecule, and convert them to regulatory cells which we know are important in controlling the disease.   MSDF So remind me whether you want more or fewer of these regulatory T cells.   Dr. Kasper It depends where you are in life. To give you sort of a circumstantial argument, we know that Firmicutes, which is that other major phyla, has been associated with a number of disease states, including obesity – just to name one – atherosclerosis, but we also know that the Firmicutes have the capacity to drive IL-17. The regulatory T cells are cells that control the IL-17 response, so it’s important to have regulatory T cells to control the IL-17. We know experimentally that IL-17 drives the experimental form of multiple sclerosis EAE, and there is mounting data – and pretty conclusive, I think – MS is probably at least in part driven by IL-17 cells. So you need these regulatory T cells to control that IL-17 response which is probably being driven by the Firmicutes population. And I’m oversimplifying this, because you remember, you’ve got a hundred trillion cells downstairs making god knows how many different metabolites with over a million genes. So what I’m presenting to you is a very simplified version of this remarkably complex organ.   MSDF So is this leading toward clinical utility for polysaccharide A?   Dr. Kasper We hope so.   MSDF Can you tell me more about that?   Dr. Kasper Well, again, our experimental data – at least in EAE – demonstrates that animals that have been induced with EAE are protected by this polysaccharide. Animals that have EAE, we can therapeutically treat them with this. So this is the first demonstration that a commensal-derived bacterial product that’s within essentially pretty much all of mankind has the capacity to induce regulatory T cells. We don’t know if MS patients are deficient in this or they have the genetic makeup that they can’t respond to it, or whatever it may be. As I said, there’s a real complexity. But the simple observation as we know is that if we take animals that are susceptible to EAE and we treat the prophylactically or therapeutically, we’re able to protect them very, very nicely against the disease process.   And now we have preliminary data in humans that we can take human cells in vitro out of a person and we can drive those human cells from an effector CD4-positive CD25-negative phenotype to a regulatory phenotype by this molecule; just five days of exposure and you see this very nice conversion that’s associated with increased IL10 protection, etc.   MSDF Do you imagine that the PSA molecule itself, if drug development goes on, is there any chemistry that needs to be done before it might possibly be therapeutic?   Dr. Kasper A lot of the chemistry has been done. We have a pretty good idea of what the molecule looks like, it’s a repeating polysaccharide chain. And we know what the conditions are at least in animals as far as innate response molecules – TLRs, toll-like receptors, etc. So as far as the molecule itself, I think we have a pretty good understanding. As I said, there’s about 20 years’ worth of very solid biology behind this molecule. So how far we are away from the clinic at this point is a matter of time, resources, and money to be able to move it from the experimental stage that we’re in into the clinic.   MSDF So you’re not the only research group working on the connection between the gut microbiome and multiple sclerosis. I wonder if you can talk a little bit about how your research fits in with the various other approaches that are going on.   Dr. Kasper Our research has been focused primarily on immune regulation – how to get the disease under control, at least experimentally and hopefully in MS patients. Most of the other labs are looking primarily at what bacteria or bacteria populations are responsible for affecting the disease; what’s driving the disease. We’ve sort of kept away from that because we were fortunate in being able to find this one molecule derived from a bacteria, as I said, that much of mankind is colonized with, so we’ve been focused mostly on how to regulate the disease rather than what’s driving the disease.   MSDF Now, as you know, there’s been a lot of talk and controversy about the role of diet in multiple sclerosis. Do you think that gut bacteria and the substances they product may provide that missing link connecting diet with MS.   Dr. Kasper I think that diet’s going to turn out to be one of the more critical environmental factors that’s associated with the disease process.   MSDF Can you say a little bit more about that?   Dr. Kasper Well, if you look at all the risk factors that we know for MS, that being genetics, obesity, smoking, gender – just to name a few – there’s about six or seven of them. Every one of those risk factors is associated with the microbiome. The common denominator for all the risk factors we know so far in MS is the microbiome, and that includes genetics. As I said, the microbiome is a two-way street; it induces things in us and we do things in turn to it, so it’s a binary system. So our speculations – and we just had a paper published in FEBs – Federation of Experimental Biology – is we’re speculating that the gut microbiome is the major environmental risk factor for MS because it includes all of the known risk factors.   So how can you adjust that? Well, the most logical way is diet, right, because it’s the change in the human diet over the last hundred years that may be accountable for the rise in the disease process. It may also be the change in the diet in Africa as well as Asia which were relatively unknown for MS, but now the incidents in Asia as well as in Africa is approaching about the same as it is in the United States and Europe. So as diet has changed, so has the incidence of the disease gone up. So I’m speculating that diet will turn out to be a very important factor in controlling the microflora, which in turn allows for the balance, the homeostasis, in individuals.   MSDF Well, very interesting. We’ve come to the end of our time, but is there anything you’d like to add, any important questions that I haven’t asked that I should have asked?   Dr. Kasper No. I think the question about the diet, you know, where do you go from here? Because it’s going to take years and years for scientists and clinicians to sort out what’s actually going on in the microbiome. We’re at the tip of the iceberg in this really, because not only is it the immunology that’s important but it’s the physiology and the physiologic changes that the gut microbiome may be creating in people. So as we get better definition of what activities are going on in the microbiome, the greater the likelihood we’ll have of understanding a whole range of human diseases. And not just MS, but that’s all other autoimmune diseases, cancer, obesity, you know, it’s a long list.   And it may ultimately turn out that it’s a clue to our understanding of cancer, for example, because as the microflora shifts as we grow older – which it does – perhaps what we’re seeing is that early on we have bacteria that induce inflammatory processes – which is why MS is a disease of young people – that tends to peter out as you get older. It’s a well-known thing. It doesn’t go away but it tends to peter out. But that may be parallel to the shift in the microflora that’s going on. So early on in the western diet you’re having mostly Firmicutes. As we get older that shifts to more of Bacteroides, which has more regulation. What does more regulation equal? Well, you’re down-regulating the immune system, and as we get older what do we become susceptible? Cancer. So there’s a real balance that’s going on here. And I think a lot of the clues to human biology as far as disease state are going to ultimately be related to the microbiome.   MSDF Dr. Kasper, thank you very much.   Dr. Kasper Thank you.   [transition music]   Thank you for listening to Episode Thirty-One of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.    [outro music]  

Abigail Salyers is a Professor of Microbiology and the G. William Arends Professor of Molecular and Cell Biology at the University of Illinois at Urbana-Champaign, and her research focuses on the ecology of microorganisms in the human body and the comings and goings of antibiotic resistance genes, particularly genes in Bacteroides species.  Dr. Salyers is ASM’s 2009 Graduate Microbiology Teaching Awardee.  If you’ve ever tried teaching or mentoring, you know it’s not always easy, but for an eminent scientist, teaching at the undergraduate or graduate level must be incredibly difficult.  After all, once you reach a certain level of knowledge in any field, it can be hard to relate your knowledge to people who know relatively little about it.  Dr. Salyers has tackled 100-level biology courses with as many as 300 students, taught one-on-one at the lab bench, and been an instructor at an intensive summer course in microbial diversity, all while rising to the top of her field in research.  In this interview, I talked with Dr. Salyers about the most influential teacher in her own life (you might be surprised to learn who that is), about whether antibiotic resistance is getting the kind of play it deserves, and about why the baboon vagina is an interesting study system.

Das Ziel der vorliegenden Arbeit war die Charakterisierung der der Rolle von T-Zellen in der Kolitis der Interleukin-2 defizienten Maus (IL-2-/-) und der Beteiligung der physiologischen Darmflora an der Pathogenese. Die Untersuchungen der mRNA-Expression im Kolon ergaben, daß die Kolitis der IL-2-/- Maus durch die Zytokine TNF-α, IFN-γ und IL-1 gekennzeichnet war, was auf eine T-Zell vermittelte Immunreaktion vom TH1-Typ schließen läßt. Ausserdem konnte mit dieser sensitiven Methode gezeigt werden, daß die Abwesenheit einer bakteriellen Darmflora zu einer drastischen Minderung der Kolits führte. Daraus kann man ableiten, daß der Einfluss der Nahrungsantigene auf die Koilitis eher gering ist, wogegen die bakterielle Darmflora den massgeblichen Stimulus für die Entstehung der Kolitis der IL-2-/- Maus darstellt. Ausserdem ist die Identifizierung der am Entzündungsgeschehen beteiligten Zytokine Voraussetzung für die Entwicklung neuer Pharmaka zur Beeinflussung dieser Mediatoren. Die durchflusszytometrischen Untersuchungen und die Analyse des Migrationsverhaltens belegten die vermehrte Einwanderung von αβTCR+CD4+ T-Zellen in das Kolon erkrankter Tiere. Eine direkte Beeinflussung von CD4+ T-Zellen könnte daher ebenfalls eine neue Therapieoption sein. Die Studien der der pathologisch gesteigerten T-Zell Einwanderung zu Grunde liegenden Mechanismen ergaben, daß dem endothelialen Addressin MAdCAM-1 eine dominante Rolle in der Lymphozytenrekrutierung in der Kolitis der IL-2-/- Maus zukommt, wogegen das Addressin VCAM-1 keine nachweisbare Beteiligung an der Vermittlung der Inflammation hat. Ferner zeigte die vorliegende Studie auch, daß die Funktion von MAdCAM-1 bei der Rekrutierung von CD4+ T-Zellen auch während der Kolitis auf das Darmkompartiment beschränkt bleibt. Dies macht MAdCAM-1 zu einer sehr interessanten Zielstruktur für einen neuartigen therapeutischen Ansatz zur Behandlung von CED. Gleichzeitig belgen die präsentierten Daten, daß eine weitgehende funktionelle Blockade der Lymphozytenrekrutierung an den Ort der Entzündung mit monoklonalen Antikörpern möglich ist. Experimente mit einer längeren Anwendungsdauer der monoklonalen Antikörper werden über die therapeutische Wirksamkeit und die Sicherheit dieser Anwendung Auskunft geben. Die Analyse der Reaktivität der interstinalen T-Zellen der IL-2-/- Maus gegenüber Antigenen der bakteriellen Darmflora ergab keinen Hinweis auf eine gesteigerte proinflammatorische Reaktivität. Durch die Etablierung von spezifischen T-Zellinien konnte im Gegenteil sogar gezeigt werden, daß trotz der massiven Inflammation des Kolons der IL-2-/- Maus T-Zellen mit potentiell antiinflammatorischem Zytokinmuster vorhanden waren. Dies widerlegte die Anfangshypothese einer pathologisch gesteigerten T-Zell Reaktivität gegenüber Antigenen der Darmflora und impliziert, daß T-Zellen nicht primär in die Krankheitsentstehung verwickelt sind, sondern sekundär aktiviert werden und daraufhin die klinische Manifestation der Kolitis vermitteln. Zukünftige Untersuchungen werden der Frage nachgehen, welche Zellen direkt von der Flora stimuliert werden und wie dies zu einer sekundären Beteiligung von T-Zellen führt. Die bedeutende Rolle der Darmflora für die Entstehung von CED kann als gesichert gelten. Für Bacteroides vulgatus lagen zu Beginn der vorliegenden Arbeit mehrere Berichte über eine Beteiligung an der Kolitis in CED-Modellen vor. Um die Beteiligung verschiedener apathogener Vertreter der physiologischen Darmflora an der Kolitisentstehung in der IL-2-/- Maus zu untersuchen, wurden Mäuse mit einem oder zwei apathogenen Keimen der Darmflora besiedelt. Diese Experimente zeigten, daß Escherichia coli alleine eine massive Kolitis auslöste, wogegen Bacteroides vulgatus keine Kolitis bewirkte und im Gegenteil sogar vor der E. coli-induzierten Kolitis schützte. Erste Arbeiten zu den hierbei beteiligten Mechanismen zeigten keine vermehrte Epitheladhärenz von E. coli in Mäusen mit Kolitis. Die Suche nach einigen bekannten E. coli-Virulenzfaktoren für den Menschen blieb negativ. Bei gleichzeitiger Anwesenheit von E. coli und B. vulgatus kamen beide Keime in erhöhter Dichte im Stuhl vor, so daß eine Kompetition um Nahrungsangebot nicht für die Verhinderung der E. coli-induzierten Kolitis durch B. vulgatus verantwortlich war. Diese Daten zeigen, daß ein vermeindlich apathogener Vertreter der Darmflora im entsprechend prädisponierten Organismus eine schwere Kolitis auslösen kann. Da die hierfür verantwortlichen Mechanismen und Virulenzfaktoren noch nicht aufgeklärt sind, mahnen die gewonnenen Erkenntnisse zu großer Sorgfalt bei der Auswahl von E. coli-Stämmen zur probiotischen Therapie. Zukünftige Arbeiten werden sich mit der Aufklärung der für die Kolitisinduktion relevanten Virulenzfaktoren von E. coli beschäftigen.