Bile Salt Hydrolase: A Microbiome Target for Enhanced Animal Health

Antibiotic growth promoters (AGP) use has been associated with the emergence of antibiotic-resistant human pathogens of animal origins. The global trend of restricting AGP necessitates the need to develop effective alternatives that will maintain safety and sustainability of food animals. Bile salt hydrolase (BSH) is an intestinal enzyme that is produced by diverse gut bacterial species and involved in host lipid metabolism. Recent studies suggest that BSH inhibitors are promising alternatives to AGP for enhanced growth performance and animal health. Using a high-purity BSH from a chicken Lactobacillus salivarius, a panel of BSH inhibitors has been identified. However, it is still unknown if these inhibitors also inhibit the function of the BSH from other bacterial species with significant sequence variation and substrate spectrum. In this study, we compared the BSH from L. salivarius to that from L. acidophilus BSH. Sequence alignment and structure modeling indicated the two BSH enzymes contain conserved catalytically important amino acid residues and domain. Using a high-purity BSH from L. acidophilus, we demonstrated that the previously identified BSH inhibitors also exhibited potent inhibitory effects on the L. acidophilus BSH. A large scale chicken experiment was conducted to examine the effect of dietary supplementation of riboflavin, a potent BSH inhibitor, on growth performance of broilers. Briefly, 300 one-day-old Hubbard broiler chicks were randomly assigned into three treatment groups (10 pens per group, 10 birds per pen) that received one of following diets: 1) a basal diet with no riboflavin added (control); 2) a basal diet + low dose of riboflavin (20 mg/kg); and 3) a basal diet + high dose of riboflavin (200 mg/kg). Dietary supplementation of riboflavin, regardless of dose, significantly increased BW gain by day 21 (P \u3c 0.0053). Significantly improved FCR was only observed for the chickens that received the low dose of riboflavin on day 21 (P \u3c 0.030). High performance liquid chromatography was used to determine the levels of riboflavin in various diets. The concentrations of total bile acids in the blood and ileal samples collected on day 14, 33, and 42 were not significantly changed in response to riboflavin treatment