Research on bile acids has increased dramatically due to recent studies demonstrating their ability to significantly impact the host, microbiome, and various disease states [1–3]. Although these liver-synthesized molecules assist in the absorption and digestion of dietary fat in the intestine, their reabsorption and recirculation also gives them access to peripheral organs [4](Fig 1A). Bile acids serve as substrates for bile acid receptors (BARs) found throughout the body that control critical regulatory and metabolic processes and therefore represent an important class of bioactive molecules [5]. Despite the importance of bile acids to host health, there remain gaps in our knowledge about the bacterial enzymes driving their composition and modification.

Members of the gastrointestinal tract (GIT) microbiota initiate bile acid metabolism via a critical first step catalyzed by bile salt hydrolases (BSHs)[6]. These enzymes hydrolyze and deconjugate the glycine or taurine from the sterol core of the primary bile acids, cholic acid (CA), and chenodeoxycholic acid (CDCA)(Fig 1B). Deconjugated bile acids can subsequently undergo a variety of microbiota-encoded transformations (ie, 7 α-dehydroxylation, dehydrogenation, and epimerization) that generate secondary bile acids, which have widespread effects on the host and resident microbiota [5, 6]. As the sole enzymes responsible for the pivotal deconjugation reaction, BSH activity serves as a gatekeeper to subsequent bile acid transformations [7]. Therefore, BSH enzymes are a promising tool for targeted manipulation of the microbiota [8]. In this Pearl, we explore what is currently known about BSH enzymes and discuss the recent work showing how their activity has the potential to impact the microbiome, host physiology, and disease outcomes in the GIT.