Human Microbiome: Trillions of Bacteria Inside You

1. Composition of the Microbiome

The gut is dominated by two bacterial phyla: Firmicutes (Lactobacillus, Clostridium, Ruminococcus) and Bacteroidetes (Bacteroides, Prevotella). Their relative ratio correlates with obesity, inflammatory bowel disease, and metabolic health.

Different body sites have distinct microbial communities. Skin harbours mostly Staphylococcus and Corynebacterium. The oral cavity has Streptococcus and Veillonella. The vaginal microbiome is typically dominated by Lactobacillus species — a protective acidic environment. Each site has adapted communities shaped by its chemistry, pH, oxygen, and immune environment.

2. How the Microbiome Develops

Humans are born nearly sterile. Colonisation begins at birth:

• Vaginal birth: Infant is colonised by mother's vaginal and fecal bacteria (Lactobacillus, Bifidobacterium). Associated with better immune development.
• C-section birth: First exposure to skin and hospital environment bacteria. Some studies link this to higher rates of asthma, allergies, and obesity in later life — though the relationship is complex.
• Breastfeeding: Human milk contains oligosaccharides (HMOs) that selectively feed Bifidobacterium, which makes the gut acidic and protective. Breast-fed infants have more diverse microbiomes.

By age 2–3, the gut microbiome reaches adult-like composition. It remains relatively stable but shifts with diet, medications, illness, and age. The elderly tend to have lower microbial diversity, associated with frailty and inflammation.

3. Gut Bacteria & Immunity

About 70% of the immune system is located in and around the gut (gut-associated lymphoid tissue, GALT). The microbiome "trains" the immune system to distinguish self vs pathogen vs harmless commensal microbe — a calibration that begins in early life.

Specific examples of immune education by gut bacteria:

• Bacteroides fragilis produces polysaccharide A, which stimulates regulatory T-cells (Tregs) — dampening excessive immune responses and protecting against inflammatory diseases.
• Short-chain fatty acids (SCFAs — see next section) produced by fermentation suppress NF-κB inflammation signalling.
• Clostridium species promote Treg differentiation in the gut, reducing susceptibility to colitis.

4. Metabolism & Short-Chain Fatty Acids

The human digestive system cannot break down dietary fibre directly — but gut bacteria can. Fermentation of fibre by Bacteroides and Firmicutes produces short-chain fatty acids (SCFAs): acetate, propionate, and butyrate.

• Butyrate: Primary fuel for colonocytes (colon cells). Anti-inflammatory via histone deacetylase inhibition. Protective against colon cancer. Species: Faecalibacterium prausnitzii, Roseburia.
• Propionate: Transported to liver, regulates gluconeogenesis and cholesterol synthesis.
• Acetate: Enters blood circulation, used as fuel by peripheral tissues, regulates hunger hormones.

Gut bacteria also synthesise vitamins K2, B12, folate, and thiamine — human cells cannot produce these. They metabolise bile acids (affecting cholesterol metabolism), drugs (altering bioavailability of medications like metformin and certain cancer drugs), and amino acids like tryptophan (precursor to serotonin).

5. The Gut-Brain Axis

The gut and brain communicate bidirectionally via the vagus nerve, immune signalling, and gut hormones — the "gut-brain axis." The enteric nervous system (gut's own nervous system) contains ~500 million neurons, comparable to a cat's brain.

Gut bacteria influence brain function through multiple routes:

• Tryptophan → serotonin: ~90% of the body's serotonin is produced in the gut by enterochromaffin cells, regulated by bacterial metabolites.
• GABA: Lactobacillus and Bifidobacterium produce GABA, the main inhibitory neurotransmitter, influencing anxiety.
• Vagus nerve: Bacteria modulate vagal afferent signalling directly to the brainstem.

In animal studies: germ-free mice show exaggerated stress responses and anxiety-like behaviour, reversed by colonisation with specific bacterial species. Human clinical trials of psychobiotics (probiotic formulations targeting mental health) are early but promising.

6. Dysbiosis & Disease

Dysbiosis — disruption of the normal microbial community — is associated with a growing list of conditions:

• IBD (Crohn's, ulcerative colitis): Reduced microbial diversity, depleted Faecalibacterium prausnitzii, excess Enterobacteriaceae.
• Obesity & Type 2 diabetes: Higher Firmicutes:Bacteroidetes ratio; reduced SCFA-producing bacteria; increased intestinal permeability ("leaky gut").
• Colorectal cancer: Enterotoxigenic Bacteroides fragilis and Fusobacterium nucleatum enrichment in tumour tissue.
• Antibiotic-associated diarrhoea: C. difficile overgrowth after broad-spectrum antibiotics kill protective bacteria.

Antibiotics cause dramatic microbiome disruption — a single course of a broad-spectrum antibiotic wipes out hundreds of species, and full recovery takes weeks-to-months. This disruption creates opportunity for pathogen colonisation.

7. Microbiome Medicine

Faecal Microbiota Transplantation (FMT): Transferring stool from a healthy donor into a patient. Highly effective (~90% success rate) for recurrent C. difficile infection — FDA approved in 2022-2023. Trials ongoing for IBD, obesity, Parkinson's, autism, and cancer.

Designer probiotics: Engineered bacteria (Lactobacillus or E. coli Nissle 1917 as chassis) that produce anti-inflammatory molecules, detect biomarkers, or secrete drugs in situ. Synlogic's SYNB1020 engineered bacterium for hyperammonaemia reached Phase 2 trials.

Dietary interventions: High-fibre diets consistently increase microbial diversity and SCFA production. Fermented foods (yogurt, kefir, kimchi) introduce live microbes and have been shown to increase microbiome diversity and reduce inflammatory markers in clinical trials.

Cancer immunotherapy: Landmark 2018 papers showed gut microbiome composition strongly predicts response to checkpoint immunotherapy (anti-PD-1). Patients with Bifidobacterium, Akkermansia, and Ruminococcaceae have better outcomes. FMT from responders to non-responders can transfer immunotherapy efficacy.