Discovering potential inhibitors for bile salt hydrolase from Lactobacillus reuteri CRL 1098 using in vitro assays and molecular docking analysis

Abstract

Bile acids deconjugation by bile salt hydrolase (BSH) enzymes is the most relevant reaction by intestinal microbiota. Currently, BSH activity is considered as a functional probiotic biomarker for its health protective effects. On the other hand, some authors have proposed the use of BSH enzyme inhibitors as an alternative to replace antibiotic growth promoters (AGP), due to their numerous adverse effects. The objetive of this study was identify potential inhibitors of the BSH enzyme from the probiotic Lactobacillus reuteri CRL 1098 (LrBSH) based on computer and in vitro design.For this, some commonly used feed additives and AGPs were tested as potential LrBSH enzyme inhibitors. Among the tested compounds, 47.11 ± 3.4% inhibition was observed with ascorbic acid, followed by citric acid (40.14 ± 1.7%), penicillin G (28.8 ± 3.5%), while the lowest inhibition percentage (9 ± 0.5%) was observed with ciprofloxacin. Besides, docking analysis revealed that caffeic acid phenethyl ester (CAPE) had lower binding energy (-7.19 kcal/mol) than the bile acid glycodeoxycholic acid, penicillin, and ascorbic acid (-6.88, -6.25, and -5.98 kcal/mol, respectively). Our results provide some new insights into the effect of a potential BSH inhibitor that could be used as alternative to AGPs.