Microbiome Interactions with Biliary Health

The biliary tract, once considered sterile, is now recognised as harbouring a complex microbiome that influences gallbladder and hepatic function. Microbial communities inhabit bile ducts, gallbladder mucus and biliary stents, interacting with bile acids, mucins and immune cells. Gut-derived bacteria can translocate into the biliary tree, modulating bile acid composition and cholesterol homeostasis, while local bile metabolites shape microbial diversity. Dysbiosis of these communities is implicated in gallstone formation, cholangitis, cholecystitis and cholangiocarcinoma. Microbial enzymes such as bile salt hydrolases and 7α-dehydroxylases alter the hydrophobicity and signalling functions of primary and secondary bile acids, thereby affecting cholesterol solubility and gallbladder motility. Host factors, including genetic variants in bile acid transporters and nuclear receptors, further mediate the effects of microbial metabolites on hepatic lipid metabolism and inflammatory pathways. Emerging evidence supports the potential of microbiome-targeted interventions—probiotics, prebiotics, faecal microbiota transplantation or small-molecule inhibitors of microbial enzymes—to restore biliary health, reduce gallstone risk and mitigate postoperative complications following cholecystectomy.

Research from Nature Portfolio

Recent studies have demonstrated that specific gut bacteria promote cholesterol gallstone formation by influencing bile acid pools and biliary cholesterol secretion. Enrichment of Desulfovibrionales correlates with increased production of secondary bile acids and heightened expression of hepatic cholesterol transporters, promoting bile supersaturation and stone nucleation. Mouse models receiving faecal transplants from gallstone-bearing donors develop cholesterol stones, underscoring a causal role for microbiota in disease onset. Earlier foundational metagenomic analyses of bile from patients with gallstone disease revealed two distinct microbial community types enriched in oral and intestinal taxa, identified novel biliary bacteria and uncovered genes encoding β-glucuronidase and multidrug efflux pumps. These discoveries have set the stage for targeted modulation of biliary microbiota to prevent or dissolve cholesterol stones.

Microbiome Interactions with Biliary Health publication trend

The graph below shows the total number of articles in microbiome interactions with biliary health across all publications each year (not limited to Nature Index journals).

Technical terms

Bile acid hydrolase: Enzyme converting conjugated bile acids to free bile acids, influencing microbial resistance and host lipid digestion.

Desulfovibrionales: Order of sulphate-reducing bacteria that produce hydrogen sulphide and modulate bile acid composition.

Faecal transplantation: Transfer of stool microbiota from a healthy donor to a recipient to restore microbial diversity and function.

Hydrophobicity of bile acids: Property determining bile acid-lipid interaction and cholesterol solubility in gallbladder bile.

Metagenomic sequencing: Culture-independent method to analyse all genomic content of microbial communities in a sample.

Secondary bile acids: Products of bacterial bile acid metabolism in the intestine that signal through host nuclear receptors.

References

1. Microbial composition associated with biliary stents in patients undergoing pancreatic resection for cancer. npj Biofilms and Microbiomes (2024).
2. Circulating vitamin levels mediate the causal relationship between gut microbiota and cholecystitis: a two-step bidirectional Mendelian randomization study. Frontiers in Nutrition (2023).
3. Cholecystectomy Significantly Alters Gut Microbiota Homeostasis and Metabolic Profiles: A Cross-Sectional Study. Nutrients (2023).
4. Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion. Nature Communications (2022).
5. Metagenomic sequencing of bile from gallstone patients to identify different microbial community patterns and novel biliary bacteria. Scientific Reports (2015).