The gut microbiota (GM) performs a range of biochemical functions that offer opportunities for precision interventions to influence host physiology. Among these, bile salt hydrolase (BSH) activity represents GM widespread and functionally diverse enzymatic processes that modulates the composition and signalling capacity of the intestinal bile acid pool. In our earlier work (PNAS, 2014), we demonstrated that specific types of microbial BSHs exert distinct effects on host physiology, revealing a class-dependent influence on bile acid metabolism and downstream signalling pathways. Subsequent investigations have expanded this understanding, showing that BSH-mediated modulation of bile acid profiles affects host metabolic health, immune function, and circadian regulation in both human studies and simplified experimental models. Indeed, the functional fallout of BSHs were elucidated at the cellular level to impact health and disease outcomes. More recently, we elucidated the molecular mechanisms underpinning BSH activity and substrate specificity (Karlov et al., 2023), providing insight into how these enzymes can be selectively targeted. Building on this foundation, we evaluated the effects of BSH inhibition on host phenotypes such as differential weight gain and nutrient utilization in broiler chickens (Geng et al., 2023), demonstrating context-dependent responses to BSH modulation. Here, we report the characterization of BSH classes response, to a suite of naturally occurring compounds capable of selective inhibition. We discuss the biochemical basis of these interactions, their functional consequences for microbial and host physiology, and their broader implications for microbiota-targeted therapeutics and nutritional interventions.