Gastroenterology
GI Microbiome
100 trillion gut bacteria — symbionts that digest, train immunity, and shape disease
The human gut harbors approximately 100 trillion microbes — bacteria, archaea, fungi, viruses — collectively the microbiome. Most are obligate anaerobes; total mass ~1-2 kg. Two dominant phyla in healthy adults — Bacteroidetes and Firmicutes — with Actinobacteria, Proteobacteria, Verrucomicrobia present at lower levels. Functions — ferment dietary fiber to short-chain fatty acids (acetate, propionate, butyrate, the colonocyte's primary fuel), synthesize vitamin K and B vitamins, deconjugate bile acids, train immune system, exclude pathogens by colonization resistance. Diversity is established in early life; cesarean delivery, formula feeding, and early antibiotics reduce diversity. Dysbiosis links to IBD, C. difficile, obesity, allergies, autism. Fecal microbiota transplant cures recurrent C. diff in >85% of cases.
- Total microbes~100 trillion (10¹⁴)
- Dominant phylaBacteroidetes, Firmicutes (~90%)
- Total mass1-2 kg
- Microbial genes100-200× human genome
- SCFAsAcetate, propionate, butyrate
- FMT for C. diff>85% cure rate
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Why microbiome matters
- C. difficile management. Recurrence rates fall with FMT.
- Antibiotic stewardship. Avoiding unnecessary antibiotics preserves flora.
- IBD pathogenesis. Dysbiosis is central to Crohn and UC.
- Liver disease. Hepatic encephalopathy treated with rifaximin and lactulose.
- Metabolic disease. Obesity, type 2 diabetes link to microbiome composition.
- Allergy and asthma. Early microbiome shapes immune development.
- Cancer immunotherapy. Response to PD-1 inhibitors correlates with gut composition.
Common errors
- Treating asymptomatic C. diff carriage. Up to 15% of inpatients colonized; only treat symptomatic disease.
- Routine probiotics in critical illness. Harm signals; not standard of care.
- Treating diarrhea with antimotility in C. diff. Loperamide may worsen toxic megacolon.
- Calling commercial microbiome tests medically useful. Not actionable; standardization lacking.
- Using PPIs without indication. Increase C. diff and pneumonia risk.
- Ignoring diet in microbiome health. Fiber intake more important than supplements.
Frequently asked questions
How does the microbiome develop?
Sterile in utero (mostly). Vaginal delivery exposes infant to maternal vaginal and fecal flora — Lactobacillus, Prevotella. Cesarean infants colonized by skin and hospital flora — different early profile. Breastfeeding selects for Bifidobacterium with HMOs (human milk oligosaccharides). By 2-3 years, microbiome adult-like and stable. Early antibiotic exposure reduces diversity and associates with allergic and metabolic disease later. The hygiene hypothesis links low microbial exposure to immune dysregulation.
What is C. difficile colitis?
Antibiotic-associated overgrowth of toxin-producing Clostridioides difficile after disruption of normal flora. Risk factors — clindamycin, fluoroquinolones, cephalosporins, PPIs, age >65, hospitalization. Watery diarrhea, fever, leukocytosis, abdominal pain. Severe cases — pseudomembranous colitis, toxic megacolon. Treat — discontinue offending antibiotic, oral vancomycin 125 mg q6h or fidaxomicin 200 mg bid for 10 days. Recurrent disease — fidaxomicin, vancomycin pulse-taper, or fecal microbiota transplant. Bezlotoxumab antibody adjunct.
How do antibiotics affect the microbiome?
Broad-spectrum antibiotics reduce diversity, eliminate sensitive species, and select resistant strains. Recovery takes weeks to months; some species may not return. Repeated courses worsen depletion. Effects link to obesity in animal models and epidemiologically in human infants. Clinical implications — narrowest spectrum effective, shortest duration, antibiotic stewardship. Not all antibiotics equal — vancomycin oral, fidaxomicin spare flora more than fluoroquinolones.
Are probiotics useful?
Mixed evidence. Reduce antibiotic-associated diarrhea modestly (Lactobacillus rhamnosus GG, Saccharomyces boulardii). Pouchitis after ileal pouch surgery responds to VSL#3. May help functional GI in subgroups. Do not prevent recurrent C. diff. Probiotics caused harm in severe acute pancreatitis trial (PROPATRIA). Caution in immunocompromised — risk of fungemia. Most over-the-counter products lack rigorous evidence; quality varies. Prebiotics (inulin, FOS) feed existing flora.
What is the gut-brain axis?
Bidirectional communication — vagal afferents, immune mediators, microbial metabolites, hormones. Microbiome may influence mood, anxiety, autism, neurodegenerative disease. Animal studies show germ-free mice have altered behavior, restored partially by microbial transfer. Human evidence emerging — fecal transplant from depressed donors transfers depression-like behavior in rodents. Specific psychobiotic strains under study but not clinically established. Promising area — early.
How does diet shape the microbiome?
Fiber feeds Bacteroidetes producing SCFAs. Fat and protein favor different communities. Mediterranean diet rich in fiber, polyphenols associates with healthier profile. Western diet (low fiber, high fat) reduces diversity. Plant-based diets shift communities within days. Artificial sweeteners (saccharin, sucralose) alter microbiome and may worsen glucose tolerance in some individuals. Long-term diet matters more than short-term swings.
What is fecal microbiota transplant?
Transfer of stool from healthy donor to patient via nasoenteric tube, colonoscopy, enema, or oral capsules. Standard for recurrent C. difficile — >85% cure rate, superior to vancomycin alone. Donors screened for infections, parasites, drug-resistant organisms. FDA enforcement discretion for C. diff; otherwise investigational. Trials in IBD, IBS, hepatic encephalopathy, autism, obesity ongoing — not yet standard. SER-109 spore preparation FDA approved 2022 for recurrent C. diff prevention.