Gut microbial bile salt hydrolase as a metabolic gatekeeper in digestive homeostasis and disease.

The gut microbiota exerts broad control over host physiology through tightly coordinated metabolic networks. Among these, bile salt hydrolase (BSH), a microbial enzyme, serves as a key mediator of microbiota-host crosstalk. As a key upstream gateway reaction in bile acid metabolism, BSH hydrolyzes conjugated bile acids and reshapes the composition and distribution of the intestinal bile acid pool. This remodeling alters bile acid signaling quality and influences the host energy metabolism, immune homeostasis and intestinal barrier integrity. In this review, we summarize the core biological functions and molecular regulatory mechanisms of microbial BSH in maintaining digestive system homeostasis. We further discuss the association between BSH dysregulation and the development of major digestive diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), inflammatory bowel disease (IBD) and colorectal cancer (CRC). Finally, we outline emerging precision strategies targeting BSH, including strain-specific probiotics, enzyme activity modulators and dietary interventions. These approaches offer a conceptual framework for microbiota-based therapies in digestive diseases.