Gut microbiota has been increasingly linked to metabolic health and diseases over the past few decades. Bile acids (BAs), the major components of bile, are bidirectionally linked to intestinal microbiota, also known as the gut microbiome-BA metabolic axis. Gut microbiota-derived bile salt hydrolase (BSH, EC 3.5.1.24), which catalyzes the “gateway” reaction in a wider pathway of bile acid modification, not only shapes the bile acid landscape, but also modulates the crosstalk between gut microbiota and host health. Therefore, microbial BSHs exhibit the potential to directly or indirectly influence microbial and host physiologies, and have been increasingly considered as promising targets for the modulation of gut microbiota to benefit animal and human health. However, their physiological functions in bacterial and host physiologies are still controversial and not clear. In this review, we mainly discuss the current evidence related to the physiological roles that BSHs played in gut microbiota and human health, and the possible underlying mechanisms. Meanwhile, we also present the potential applications of BSHs and BSH-producing probiotics in various fields. Finally, we describe several important questions that need to be addressed by further investigations. A detailed exploration of the physiological significance of BSHs will contribute to their future diagnostic and therapeutic applications in improving animal and human health.

Lignocellulosic ethanol could offer a sustainable source to meet the increasing worldwide demand for fuel. However, efficient and simultaneous metabolism of all types of sugars in lignocellulosic hydrolysates by ethanol-producing strains is still a challenge. An engineered strain Escherichia coli B0013-2021HPA with regulated glucose utilization, which could use all monosaccharides in lignocellulosic hydrolysates except glucose for cell growth and glucose for ethanol production, was constructed. In E. coli B0013-2021HPA, pta-ackA, ldhA and pflB were deleted to block the formation of acetate, lactate and formate and additional three mutations at glk, ptsG and manZ generated to block the glucose uptake and catabolism, followed by the replacement of the wild-type frdA locus with the ptsG expression cassette under the control of the temperature-inducible λ pR and pL promoters, and the final introduction of pEtac-PA carrying Zymomonas mobilis pdc and adhB for the ethanol pathway. B0013-2021HPA was able to utilize almost all xylose, galactose and arabinose but not glucose for cell propagation at 34 °C and converted all sugars to ethanol at 42 °C under oxygen-limited fermentation conditions. Engineered E. coli strain with regulated glucose utilization showed efficient metabolism of mixed sugars in lignocellulosic hydrolysates and thus higher productivity of ethanol production.