Bile Salt Hydrolase Activity in Gut Microbiome Dynamics

Bile salt hydrolases (BSHs) are microbial enzymes that initiate the deconjugation of host-derived bile acids, thereby modulating the composition and signalling properties of the intestinal bile acid pool. This deconjugation alters solubility and receptor activation, influencing lipid digestion, energy homeostasis and immune regulation. Recent advances have revealed that BSHs not only cleave glycine and taurine moieties but also catalyse amine conjugation, yielding novel bile acid amidates with distinct bioactivities. Structural studies have identified substrate-selective loops that determine glycine versus taurine specificity, providing a molecular framework for engineering probiotic strains. Through shaping the bile acid milieu, BSH-expressing commensals can restrict the germination and growth of pathogens such as Clostridioides difficile, impact colon tumourigenesis and influence enterohepatic circulation. The global distribution of BSH genes underlies population-specific variations in bile acid profiles, with implications for therapeutic modulation of host metabolism and disease risk.

Research from Nature Portfolio

Discoveries in 2024 have established that BSHs possess a dual enzymatic function, acting as amine N-acyltransferases that conjugate diverse amines to deconjugated bile acids. This activity generates bacterial bile acid amidates that engage host receptors, including the pregnane X receptor and aryl hydrocarbon receptor, thereby linking microbial metabolism with transcriptional control of detoxification pathways.

Structural analyses reported in 2023 have pinpointed a flexible loop region within Lactobacillaceae BSHs that governs substrate specificity for glycine or taurine conjugates. By correlating loop sequence variation with deconjugation kinetics, researchers have elucidated how distinct BSH orthologues sculpt the bile acid landscape, reinforcing colonisation resistance against C. difficile through selective depletion of conjugated bile acids required for spore germination.

Also in 2023, investigation into Bacteroides-derived BSH revealed a pro-carcinogenic axis in obesity-related colorectal cancer models. High BSH activity increased local concentrations of deoxycholic and lithocholic acids, activated G-protein-coupled bile acid receptors and stimulated β-catenin-driven chemokine expression, thereby fostering an immunosuppressive tumour microenvironment. Pharmacological inhibition of BSH attenuated tumour progression under a high-fat diet, highlighting BSH as a therapeutic target.

Bile Salt Hydrolase Activity in Gut Microbiome Dynamics publication trend

The graph below shows the total number of articles in bile salt hydrolase activity in gut microbiome dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Bile salt hydrolase (BSH): Microbial enzyme that cleaves glycine or taurine from conjugated bile acids, initiating their transformation.

Conjugated bile acids: Bile acids linked to amino acids (glycine or taurine) in the liver, aiding solubility and emulsification of lipids.

Deconjugation: Enzymatic removal of amino acid moieties from bile acids, altering their chemical properties and biological activities.

Enterohepatic circulation: Recycling pathway in which bile acids are secreted into the intestine, reabsorbed and returned to the liver for reuse.

References

1. Bile salt hydrolase catalyses formation of amine-conjugated bile acids. Nature (2024).
2. Taxonomic identification of bile salt hydrolase‐encoding lactobacilli: Modulation of the enterohepatic bile acid profile. iMeta (2023).
3. Bile salt hydrolases shape the bile acid landscape and restrict Clostridioides difficile growth in the murine gut. Nature Microbiology (2023).
4. Bile salt hydrolase in non-enterotoxigenic Bacteroides potentiates colorectal cancer. Nature Communications (2023).
5. Bacteroides fragilis alleviates necrotizing enterocolitis through restoring bile acid metabolism balance using bile salt hydrolase and inhibiting FXR-NLRP3 signaling pathway. Gut Microbes (2024).
6. Taxonomic profiling and populational patterns of bacterial bile salt hydrolase (BSH) genes based on worldwide human gut microbiome. Microbiome (2019).