senior sem presentation

Providing Colonization Resistance

Microbes compete with pathogens for nutrients and physical space to create resistance and prevent harmful bacteria from invading

Executing Metabolic Conversions

break down organic and inorganic matter, turning complex substrates into energy, biomass, and metabolic byproducts

Maintaining Gut-Immune Cross-Talk

producing essential metabolites that regulate immune cell activity and reinforce the intestinal barrier

Butyrate (fuel, shield, peacekeeper)

Fuel: Serves as the primary energy source for colon cells, keeping the gut lining oxygen-depleted (hypoxic) to sustain beneficial bacteria

Shield: Signals gut cells to build tighter walls and produce mucus, preventing "leaky gut."

Peacekeeper: Acts as a histone deacetylase (HDAC) inhibitor to drive Regulatory T cell (Treg) development, turning down unneeded inflammation.

Propionate (where, metabolic control, systemic dampening)

Liver Transport: Travels through the portal vein directly to the liver.

Metabolic Control: Helps regulate hepatic cholesterol synthesis, lipid metabolism, and blood sugar balance.

Systemic Dampening: Migrates to bone marrow to suppress the overproduction of inflammatory immune cells.

Acetate (Abundance & Circulation, Cross-Feeding, Appetite & Signaling)

Abundance & Circulation: Produced in the largest quantities and circulates broadly through the bloodstream to peripheral tissues, muscle, and the brain.

Cross-Feeding: Acts as a vital nutrient fuel that secondary microbes consume to manufacture more butyrate.

Appetite & Signaling: Crosses the blood-brain barrier to help regulate hypothalamic appetite pathways and influence immune cell migration.

enzymes that participate in the production of secondary bile acids

Bile Salt Hydrolase (BSH), 7α/β-Dehydroxylase

Deoxycholic Acid (DCA): FXR + metabolic crosstalk

FXR Activation: Highly potent activator of the Farnesoid X Receptor (FXR) in the intestine and liver, tightly regulating host cholesterol synthesis, liver bile acid production, and triglyceride homeostasis

Metabolic Crosstalk: Influences systemic energy expenditure, glucose metabolism, and lipid handling.

Lithocholic Acid (LCA): TGR5 signaling + Treg induction

1. TGR5 Signaling: Acts as a potent agonist for the cell-surface receptor TGR5, expressed on immune cells (like macrophages) and intestinal cells.

   1. Suppresses pro-inflammatory cytokine production in macrophages and modulates mucosal immunity.

2. Treg Induction: Specialized derivatives of LCA can promote the differentiation of Regulatory T cells (Tregs), contributing to immune tolerance in the gut.

NF-kappaB

primary master-switch for inflammation. By blocking NF-kappaB, these metabolites act as chemical peacekeepers

how can microbiomes produce vitamins?

genomes contain genes encoding enzymes for de novo biosynthesis or salvage pathways.

De novo synthesis vs Salvage

de novo: The bacterium builds the vitamin essentially from basic metabolic precursors

salvage: The bacterium takes an already partially formed vitamin or vitamin intermediate from the environment and modifies/recycles it

Vitamin K2

Crucial for activating proteins involved in normal blood coagulation and bone mineralization

B-Vitamins:

Act as indispensable coenzymes for cellular energy production (Krebs cycle), DNA synthesis, and optimal nervous system function

MAMPs why called that?

describing molecular signatures found on microbes that are recognized by host immune systems

Intestinal Permeability ("Leaky Gut") Triggers Systemic Autoimmune Inflammation

1. dysbiosis weakens tight junction proteins and degrades the protective mucus layer

2. Structural microbial components (like Lipopolysaccharide [LPS]) breach the gut barrier and enter circulation —> continuously activating systemic pattern recognition receptors (TLR4) —> immune system becomes more easily triggered to mistakenly attack the body's own healthy cells

Molecular Mimicry Drives Autoreactive Cell Activation

1. mimic in structural shape or amino acid sequence

2. Immune cells (T and B cells) trained to attack bacterial proteins cross-react with human tissues, causing misdirected, targeted autoimmune attacks on healthy organs

TH17 / Treg Imbalance Promotes Autoimmune Destruction

1. stimulates the overproduction of pro-inflammatory TH17 cells and IL-17 signaling.

2. Shifts the systemic immune balance away from autoimmune suppression (Tregs) and toward active tissue destruction, fueling the onset and progression of autoimmune diseases

Rheumatoid Arthritis (RA)

Gut/Oral Connection: Specific bacteria in the oral cavity and gut drive protein citrullination

Autoimmune Outcome: Triggers anti-citrullinated protein antibody (ACPA) production

what does ACPA stand for?

anti-citrullinated protein antibody

Citrullination

ACPAs bind to their targets (citrulline) → The ACPA attaches to a citrullinated protein → creates an antigen–antibody complex, also called an immune complex. →  Immune complexes activate inflammation → causes immune cells to release inflammatory signals

Systemic Lupus Erythematosus (SLE)

Bacterial translocation = Gut bacteria/bacterial products → cross the intestinal lining → enter circulation

turns up the immune response and autoantibody production , impacting skin, joints, kidneys, brain, and other organs 

Multiple Sclerosis (MS):

Less SCFAs → less immune regulation → greater potential for inflammatory immune responses → fail to calibrate systemic immune responses → “wonky T cells”

 T cells  attacking the myelin sheath of central nervous system neurons → inflammation damages the myelin sheath surrounding neurons. → Damaged myelin disrupts normal nerve-signal transmission

Inflammatory Bowel Disease (IBD - Crohn's & Ulcerative Colitis)

Less SCFA → weaker epithelial barrier + less immune regulation

Beneficial bacteria ↓ → competition decreases → pathobionts ↑ expanded bacteria can produce microbial molecules that activate immune receptors, increasing inflammatory signaling -> chronic inflammation of the mucosal barrier