Primary to Secondary: A Microbial Transformation
The liver synthesises primary bile acids — cholic acid and chenodeoxycholic acid — from cholesterol and conjugates them with glycine or taurine before secreting them into the duodenum via the common bile duct. Their primary function is to emulsify dietary fats for absorption. But the story does not end there. In the colon, anaerobic bacteria deconjugate and transform primary bile acids into secondary bile acids — deoxycholic acid (DCA) and lithocholic acid (LCA) — through 7α-dehydroxylation reactions performed primarily by Clostridium clusters XIVa and XI.
Signalling Beyond Digestion
Secondary bile acids are not waste products. They are potent signalling molecules that activate two major receptor systems:
Farnesoid X receptor (FXR): Activated predominantly by chenodeoxycholic acid and its conjugates, FXR regulates bile acid synthesis through a negative feedback loop, modulates hepatic lipogenesis and gluconeogenesis, and influences intestinal barrier integrity. FXR activation in the intestine triggers fibroblast growth factor 19 (FGF19) release, which signals to the liver to reduce bile acid production.
Takeda G protein-coupled receptor 5 (TGR5): Activated by secondary bile acids (particularly LCA), TGR5 stimulates GLP-1 secretion from enteroendocrine L-cells (improving glucose homeostasis), modulates immune cell function (promoting anti-inflammatory macrophage polarisation), and influences colonic motility.
Bile Acid Diarrhoea
Approximately 30 percent of patients diagnosed with IBS-D (diarrhoea-predominant IBS) actually have bile acid malabsorption (BAM), where excessive bile acids reach the colon and stimulate water and electrolyte secretion, accelerating transit. SeHCAT scanning or serum C4 measurement can identify BAM, and bile acid sequestrants (cholestyramine, colesevelam) are effective treatments. This represents one of the most underdiagnosed causes of chronic diarrhoea.
The Gut-Liver-Microbiome Triangle
Disruption of bile acid metabolism has implications beyond the gut. In non-alcoholic fatty liver disease (NAFLD), altered microbial bile acid metabolism shifts the FXR signalling balance, promoting hepatic fat accumulation and inflammation. Conversely, antibiotic-induced microbiome disruption reduces secondary bile acid production, impairing metabolic signalling. This triangular relationship — liver, microbiome, and bile acids — is increasingly recognised as a therapeutic target.
Dietary Influence
A high-fat diet increases total bile acid secretion and shifts the bile acid pool toward more hydrophobic (and potentially cytotoxic) species. Fibre-rich diets, by contrast, bind bile acids in the lumen and promote their faecal excretion, stimulating de novo synthesis from cholesterol — one mechanism by which dietary fibre lowers circulating cholesterol levels. The microbiome mediates this effect: without colonic bacteria, bile acid transformation and its downstream signalling would not occur.