Podcast
Questions and Answers
Which type of immune response is primarily associated with CD 8 T lymphocytes?
Which type of immune response is primarily associated with CD 8 T lymphocytes?
What effect do microorganism-derived secondary bile acids generally have?
What effect do microorganism-derived secondary bile acids generally have?
What does colonization resistance primarily prevent?
What does colonization resistance primarily prevent?
Which cytokine is known to increase in response to the activities of bile acids?
Which cytokine is known to increase in response to the activities of bile acids?
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What therapeutic approach attempts to reshape the microbiota in sick individuals?
What therapeutic approach attempts to reshape the microbiota in sick individuals?
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Where do the majority of bacterial taxa reside within the gastrointestinal tract?
Where do the majority of bacterial taxa reside within the gastrointestinal tract?
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What role do metabolites produced by bacteria play in relation to host physiology?
What role do metabolites produced by bacteria play in relation to host physiology?
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Which class of bacteria is known to increase T regulatory cells through the production of SCFA?
Which class of bacteria is known to increase T regulatory cells through the production of SCFA?
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Which of the following is NOT a known metabolite produced by bacteria in the gastrointestinal tract?
Which of the following is NOT a known metabolite produced by bacteria in the gastrointestinal tract?
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What beneficial effect do Segmented Filamentous Bacteria (SFB) have on the host?
What beneficial effect do Segmented Filamentous Bacteria (SFB) have on the host?
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What is the role of microbiota in relation to the immune system?
What is the role of microbiota in relation to the immune system?
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Which factor is NOT mentioned as a driver for changes in microbiome configuration in industrialized settings?
Which factor is NOT mentioned as a driver for changes in microbiome configuration in industrialized settings?
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What method is suggested for studying candidate interactions between microbiota and immune features?
What method is suggested for studying candidate interactions between microbiota and immune features?
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How can beneficial aspects of the microbiota absent in western guts potentially be restored?
How can beneficial aspects of the microbiota absent in western guts potentially be restored?
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In terms of lifestyle-related immune disorders, what should be the primary focus in studies comparing microbial populations?
In terms of lifestyle-related immune disorders, what should be the primary focus in studies comparing microbial populations?
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What is the significance of longitudinal intervention studies in microbiota-immune research?
What is the significance of longitudinal intervention studies in microbiota-immune research?
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In studying ancestral microbiomes compared to industrialized settings, what aspect is typically observed?
In studying ancestral microbiomes compared to industrialized settings, what aspect is typically observed?
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What is a primary goal of the suggested models for understanding microbial communities?
What is a primary goal of the suggested models for understanding microbial communities?
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Which of the following bacteria is associated with Gram-negative, enteric pathogens?
Which of the following bacteria is associated with Gram-negative, enteric pathogens?
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What role do colonocytes play in the intestinal environment?
What role do colonocytes play in the intestinal environment?
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What is a potential consequence of antibiotic pressure on the microbiota?
What is a potential consequence of antibiotic pressure on the microbiota?
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Which of the following statements is true regarding direct vs indirect colonization resistance?
Which of the following statements is true regarding direct vs indirect colonization resistance?
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Which of the following pathogens is known for its resistance to vancomycin?
Which of the following pathogens is known for its resistance to vancomycin?
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How does the epithelial barrier function in relation to infections?
How does the epithelial barrier function in relation to infections?
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Which fermentation product is affected by changes in microflora due to antibiotic treatment?
Which fermentation product is affected by changes in microflora due to antibiotic treatment?
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What is a potential benefit of using selective probiotics in colonization resistance?
What is a potential benefit of using selective probiotics in colonization resistance?
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Study Notes
Microbiota and Immune Response
- Microbiota and immune system co-evolved over 100 million years.
- Associated with both local and systemic immune responses, signaling, and regulation.
- play a role in responses to cancer immunotherapies and precision therapies.
- Gut microbiota plays a role in shaping and maintaining the immune system both innate and adaptive.
- Symbiotic relationship between organisms living together.
- Gut microbiota increases metabolism in the host (10% calories from diet).
- Produces vitamins (B2, B12, K, and folic acid)
- Protects against colonization by pathogenic bacteria.
- Produce pathogen-associated molecular patterns (PAMPs).
- Regulate intestinal immune responses.
- PAMPs are recognized by pattern recognition receptors (PRRs).
Gut Microbiota in Health
- Microbiota interaction leads to B cell switch to IgA, regulatory T cell induction, and T cell differentiation to Th17.
- Commensal bacteria induce CD4+T cell differentiation.
- Naïve CD4+T cells differentiate into four major cell types: Th1, Th2, Tregs, and Th17.
- Once differentiated, each lineage produces cytokines and perform specific functions.
- Commensal bacteria produce antimicrobial peptides.
- Compete for nutrients and adhere to the attachment sites.
- Prevents attachment and subsequent entry of pathogenic bacteria, protects epithelial cells.
Protective Function (Barrier Effect)
- Competes for attachment sites in the brush border of the intestinal epithelial cells.
- Competes for available nutrients.
- Produces antimicrobial peptides (bacteriocins).
Intestinal Barrier Importance
- The barrier pattern is important for the normal development of the immune system
- It isn't only for pathogenic bacteria, but commensal bacteria too.
Pursuing Human-relevant Gut Microbiota-Immune Interactions
- Methods for studying microbiota-immune interactions in humans.
- Longitudinal intervention studies in humans.
- Starting with a cohort of participants.
- Lifestyle intervention that perturbs the microbiota (diet, weight loss, antibiotic use)
- Monitor microbiota and immune system profiling over time.
- Use machine learning for identification of candidate interactions.
- Investigate interactions in mouse models and in vitro to understand mechanistic underpinnings.
Traditional vs. Industrialized Population Studies
- Identifying microbes relevant to lifestyle-related immune disorders.
- Comparing microbiomes of individuals with different lifestyles, focusing on shared characteristics that vary with industrialization rather than geographical location.
Industrialized vs Ancestral Microbiomes Ecological Model
- Ancestral microbiomes: more diverse, fiber degrading.
- Industrialized microbiomes: less diverse, mucus degrading, more inflammatory.
- Dietary changes, antibiotic use, and increased sanitation influence microbiota composition.
- Dietary changes, strain reintroduction, and Fecal Microbiota Transplant (FMT) for restoration of beneficial aspects.
The Gastrointestinal Tract
- Bacteria colonize the large intestine, sometimes preferentially colonizing the intestinal lumen, mucus or intestinal crypts.
- Different species of bacteria have different genetic components, and express genes differently to process various substrates and produce distinct metabolites.
Host Immunity and Diversity
- Host immunity plays a central role in shaping microbiota diversity.
Segmented Filamentous Bacteria (SFB)
- Interactions with host immunity due to metabolite production.
- Affecting Th17 and IgA response.
- Intestinal barrier function, colonization resistance, systemic anti-fungal, and antibacterial effects.
- Clostridium spp. increases SCFAs and causes a rise in T regulatory cells.
- Bacteria in colon mucosa causes anti-infectious and anti-tumour immune response via CD8 T lymphocytes.
- Adaptive cellular and humoral immune response from B cells.
Bile Acids
- Bile acids have secondary anti-inflammatory properties, generally acting through cytokines.
- Increase in IL-10
- Decrease in IL-12 and TNF-alpha leads to increased tolerance.
Preventing and/or Curative
- Diseases, infections, and chronic conditions (Type 1-2 D, obesity, and cancer) result or are caused by problems in immune regulation and chronic inflammation.
- VANISH (Volatile and/or Associated Negatively with Industrialized Societies of Humans) taxa.
- Civilization/industrialization predisposes people to inflammatory diseases related to the immune system and gut microbiome.
Therapeutic Approaches
- The degree to which diet and other lifestyle interventions are able to manipulate the microbiota is open to question.
- Promising data exists in human studies suggesting interventions can be useful therapeutic interventions.
- Exploring other tools such as engineered microbes or delivery of microbially-derived metabolites and requirements to introduce change in microbiota.
- Possible changes in the host immune environment.
Colonization Resistance
- Prevention of pathogenic bacteria invasion.
- Inhibition of endogenous bacteria overgrowth which are present at a certain amount.
- Protection against enteric pathogens.
- Discovered by studying increased susceptibility to enteric pathogens under the influence of antibiotics.
- Reshape a healthy microbiota in sick persons by fecal microbiota transplantation (FMT).
- Various forms of commensal anaerobic bacteria and their roles in barrier formation against enteric pathogens.
Colonocytes (Epithelial cells in the colon)
- Ecologically, the immune and microbiota systems co-evolved for beneficial mechanisms.
- Colonocytes maintain physiological homeostasis by shaping the microbiota.
Antibiotic Pressure
- Fermentation produces reduction in gut microflora and SCFA.
- Failure to preserve epithelial hypoxia.
- Decreased Treg triggering.
- Increased inflammation.
Gut Microbiota and Disease
- The gut microbiota significantly influences how the immune system responds when there is health vs. disease.
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Description
Test your knowledge on the interactions between the microbiota and the immune response. This quiz covers topics including CD 8 T lymphocytes, bile acids, colonization resistance, and the therapeutic approaches to reshape microbiota. Understand the crucial role of gut bacteria in host physiology and immune system function.
