Microbiota and Immune Response Quiz

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.