Microbiota in health and disease

At a glance

• The gut holds about 4 × 10¹³ bacteria, roughly as many as human cells, mostly anaerobes in the colon.
• Density rises down the gut: about 10¹ to 10³ per mL in the stomach, 10⁴ in the jejunum, 10⁷ to 10⁸ in the terminal ileum, 10¹¹ to 10¹² per gram in the colon. Acid, bile, motility and the ileocaecal valve keep the small bowel sparse.
• The dominant phyla are Bacillota (Firmicutes) and Bacteroidota (Bacteroidetes).
• Functions examiners ask about: short-chain fatty acids, bile acid metabolism, colonisation resistance, vitamin K synthesis, and drug metabolism.
• Dysbiosis explains C. difficile infection, small intestinal bacterial overgrowth (SIBO), hepatic encephalopathy and D-lactic acidosis. Links to IBD, IBS, obesity and cardiovascular disease are mostly associations.

What the microbiota does

Function	Mechanism	Clinical link
Short-chain fatty acids	Fibre fermented to acetate, propionate and butyrate	Butyrate feeds colonocytes; diversion colitis when the faecal stream is diverted
Bile acid metabolism	Deconjugation and 7α-dehydroxylation to secondary bile acids	Loss after antibiotics permits C. difficile; deconjugation in SIBO causes fat malabsorption
Colonisation resistance	Competition for nutrients and niches, bacteriocins, secondary bile acids	Antibiotics open the niche for C. difficile, VRE, Candida
Vitamins	Vitamin K2 (menaquinones) and some B vitamins	INR rises when antibiotics are given with warfarin
Immune education	Butyrate and polysaccharide A induce regulatory T cells; segmented filamentous bacteria drive Th17	Dysbiosis in IBD
Ammonia generation	Urease-producing bacteria split urea	Hepatic encephalopathy

Mechanisms behind clinical findings

C. difficile after antibiotics

Commensal clostridia convert primary bile acids (cholate, taurocholate) to secondary bile acids (deoxycholate, lithocholate). Taurocholate triggers spore germination; secondary bile acids inhibit vegetative growth. Broad-spectrum antibiotics, particularly clindamycin, cephalosporins, fluoroquinolones and amoxicillin-clavulanate, deplete those commensals, so spores germinate and toxins A and B are produced. Treatment with vancomycin or fidaxomicin doesn't restore the community, which is why about 20 to 25% recur. See acute infectious diarrhoea.

Small intestinal bacterial overgrowth

Risk comes from stasis (strictures, blind loops, diverticula, scleroderma, diabetic autonomic neuropathy), loss of the valve (ileocaecal resection) and loss of acid (long-term PPIs, gastrectomy). The overgrowth causes:

• B12 deficiency, as bacteria consume B12 before the ileum, with normal or high folate, because bacteria synthesise it
• Steatorrhoea from bile acid deconjugation
• Bloating from carbohydrate fermentation, detected by a rise in breath hydrogen or methane after glucose or lactulose

Hepatic encephalopathy

Colonic bacteria make ammonia from urea and protein. A cirrhotic liver and portosystemic shunts let it reach the brain, where astrocytes convert it to glutamine and swell.

• Lactulose is fermented to lactic and acetic acid. Colonic pH falls, ammonia (NH₃) becomes ammonium (NH₄⁺), which can't cross the mucosa, and the osmotic effect clears it.
• Rifaximin is a poorly absorbed rifamycin that reduces ammonia-producing bacteria. It is added after recurrence.

See cirrhosis and chronic liver disease.

Worked example: D-lactic acidosis

A 52-year-old woman with short bowel syndrome after mesenteric ischaemia becomes confused and ataxic after a large carbohydrate meal.

• Na 140, Cl 106, HCO₃ 14 mmol/L
• Anion gap = 140 − (106 + 14) = 20 mmol/L (raised)
• L-lactate 1.1 mmol/L, ketones negative, creatinine normal, no toxic alcohols

The unexplained gap is D-lactate. Undigested carbohydrate reaches a colon with an overgrowth of lactobacilli, which ferment it to D-lactate. Humans metabolise D-lactate slowly, and standard lactate assays measure only the L-isomer. Treatment is bicarbonate, carbohydrate restriction, and sometimes oral antibiotics.

The microbiota and drugs

Drug	Bacterial action	Effect
Sulfasalazine, balsalazide, olsalazine	Azoreductases cleave the azo bond	Releases active 5-ASA in the colon
Digoxin	Eggerthella lenta reduces it to inactive dihydrodigoxin	Macrolides kill E. lenta and raise digoxin levels
Irinotecan	Bacterial β-glucuronidase reactivates SN-38 from its glucuronide	Delayed severe diarrhoea
Levodopa	Bacterial decarboxylation (Enterococcus)	Less drug reaches the brain
Warfarin	Antibiotics reduce vitamin K2 synthesis (plus CYP inhibition)	INR rises

TMAO: gut bacteria convert dietary choline and carnitine (red meat, eggs) to trimethylamine, which the liver oxidises to TMAO. High levels are associated with cardiovascular events, but causality isn't proven.

Faecal microbiota transplantation and probiotics

• In van Nood 2013, duodenal donor faeces cured recurrent C. difficile in 81% after one infusion versus 31% with vancomycin alone. Colonoscopic delivery gives cure rates around 90%.
• In Australia FMT is regulated by the TGA as a biological. BiomeBank's Biomictra is ARTG-registered and its conditions of registration restrict it to C. difficile infection (in practice recurrent or refractory disease, per guidelines), prescribed under the supervision or advice of a gastroenterologist or infectious diseases physician. Colonoscopic delivery is preferred; enema or upper GI delivery can be used if colonoscopy is contraindicated or the patient is frail. FMT for IBD, IBS or obesity is possible only in a registered trial, under the Special Access Scheme or through an Authorised Prescriber.
• The ASID 2025 guideline places FMT after recurrence despite appropriate antibiotics.
• Bezlotoxumab, the anti-toxin B antibody once used to prevent recurrence, was withdrawn by its manufacturer in 2025.
• Donor screening matters: in 2019 two immunocompromised recipients developed ESBL E. coli bacteraemia from an unscreened donor stool, and one died.
• Probiotics aren't routinely recommended for preventing C. difficile in Australian guidance. Saccharomyces and Lactobacillus cause fungaemia and bacteraemia in patients with central lines or immunosuppression.

How it's tested

• Explaining a lab pattern: low B12 with high folate, or a high anion gap with normal lactate.
• Mechanism of lactulose or rifaximin in hepatic encephalopathy.
• Why antibiotics precipitate C. difficile and why it recurs.
• Drug interactions involving gut bacteria (digoxin and clarithromycin, sulfasalazine activation).
• Where FMT fits, and its risks.

Pitfalls

• Pitfall: attributing high folate with low B12 to folate supplements and missing SIBO.
• Routine lactate doesn't detect D-lactate. Ask for it specifically.
• Rifaximin is an add-on to lactulose for recurrent encephalopathy, not a replacement.
• Most microbiome-disease links (IBS, obesity, TMAO) are associations. Don't present them as established causes.
• Probiotics are not harmless in patients with central lines or severe immunosuppression.