Gastrointestinal microbiome

Gastrointestinal microbiome

Gastrointestinal microbiome

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GI Microbiome - The Gut Garden

Gut Microbiome: Homeostasis vs. Dysbiosis

  • Composition: Predominantly anaerobic bacteria. Key phyla: Bacteroidetes (G-), Firmicutes (G+). ↑Firmicutes/Bacteroidetes ratio linked to obesity.
  • Core Functions:
    • Metabolic: Ferments fiber into Short-Chain Fatty Acids (SCFAs). Synthesizes Vitamin K and B vitamins (biotin, folate).
    • Immune: Competitively inhibits pathogens. Essential for maturing Gut-Associated Lymphoid Tissue (GALT).
  • Dysbiosis (Imbalance):
    • Antibiotics (e.g., clindamycin) risk Clostridioides difficile overgrowth.
    • Associated with IBD, obesity, and allergies.

⭐ Butyrate, a key SCFA, is the primary fuel for colonocytes and has anti-inflammatory effects.

Core Functions - Microbial Metabolism

  • Carbohydrate Fermentation:
    • Anaerobic breakdown of indigestible dietary fiber (e.g., cellulose, pectin) into Short-Chain Fatty Acids (SCFAs).
    • Key SCFAs:
      • Butyrate: Preferred energy source for colonocytes; strengthens gut barrier.
      • Propionate: Hepatic gluconeogenesis substrate.
      • Acetate: Enters peripheral circulation; used in muscle & adipose tissue.
  • Vitamin Synthesis:
    • Production of essential vitamins unavailable from diet alone.
    • Includes Vitamin K (crucial for coagulation factors) and B vitamins like Biotin (B7) and Folate (B9).
  • Bile Acid Metabolism:
    • Deconjugation and conversion of primary bile acids into secondary bile acids (e.g., deoxycholic acid).

⭐ Gut microbiota can metabolize and inactivate drugs, altering bioavailability. A classic example is the bacterial inactivation of Digoxin, reducing its therapeutic effect in susceptible individuals.

Eubiotic vs. Dysbiotic Microbiota and Metabolic Products

Dysbiosis - When Flora Fails

  • Definition: Disruption of the normal gut microbial community's composition, function, or diversity, often triggered by antibiotics, diet, or illness.
  • Classic Example: Clostridioides difficile Infection
    • Antibiotic use (esp. clindamycin, cephalosporins, fluoroquinolones) depletes protective flora, allowing C. diff overgrowth.
    • Toxin A (enterotoxin) and Toxin B (cytotoxin) lead to mucosal injury, inflammation, and formation of pseudomembranes.
    • Results in profuse, watery diarrhea, abdominal cramping, and potential toxic megacolon.
  • Therapeutic Interventions
    • Probiotics: Administration of live beneficial bacteria (e.g., Lactobacillus).
    • Prebiotics: Substrates (e.g., inulin) that promote growth of beneficial bacteria.
    • Fecal Microbiota Transplant (FMT): Highly effective for recurrent C. diff by restoring a healthy, diverse microbiome.

⭐ Diagnosis of C. difficile relies on detecting toxins A/B in the stool via enzyme immunoassay (EIA) or nucleic acid amplification tests (NAAT).

Endoscopic view of pseudomembranous colitis

Therapeutics - Gut Reset Button

  • Antibiotics: Broad-spectrum use disrupts flora → dysbiosis, ↑ risk of C. difficile infection (CDI).
  • Probiotics: Live beneficial bacteria (Lactobacillus, Bifidobacterium) to restore balance. Limited efficacy for severe dysbiosis.
  • Prebiotics: Dietary fibers (e.g., inulin) that fuel beneficial microbes, promoting a healthy gut environment.
  • Fecal Microbiota Transplant (FMT): Infusion of stool from a healthy donor to restore a complex, healthy microbiome.

⭐ Fecal Microbiota Transplant (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection, with cure rates often exceeding 90%.

Fecal Microbiota Transplant (FMT) Procedure Diagram

  • Anaerobes like Bacteroides and Clostridium are the most predominant organisms in the colon.
  • Gut flora are a primary source of Vitamin K and several B vitamins.
  • They are essential for the metabolism of bile acids and the breakdown of bilirubin.
  • Provide colonization resistance against pathogens, most notably C. difficile.
  • Crucial for the development and maturation of gut-associated lymphoid tissue (GALT).
  • Antibiotic use disrupts this barrier, increasing infection risk.

Practice Questions: Gastrointestinal microbiome

Test your understanding with these related questions

A 47-year-old man comes to the physician because of abdominal pain and foul-smelling, watery diarrhea for several days. He has not had nausea, vomiting, or blood in the stool. He has a history of alcohol use disorder and recently completed a 7-day course of clindamycin for pneumonia. He has not traveled out of the United States. Which of the following toxins is most likely to be involved in the pathogenesis of this patient's symptoms?

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Flashcards: Gastrointestinal microbiome

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Developed countries purify their _____ supply, eliminating HAV infection risk (fecal-oral transmission)

TAP TO REVEAL ANSWER

Developed countries purify their _____ supply, eliminating HAV infection risk (fecal-oral transmission)

water

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