Identification and Characterization of a Bile Salt Hydrolase from Lactobacillus salivarius for Development of Novel Alternatives to Antibiotic Growth Promoters

Abstract

bAntibiotic growth promoters (AGPs) have been used as feed additives to improve average body weight gain and feed efficiency in food animals for more than 5 decades. However, there is a worldwide trend to limit AGP use to protect food safety and public health, which raises an urgent need to discover effective alternatives to AGPs. The growth-promoting effect of AGPs has been shown to be highly correlated with the decreased activity of intestinal bile salt hydrolase (BSH), an enzyme that is produced by various gut microflora and involved in host lipid metabolism. Thus, BSH inhibitors are likely promising feed additives to AGPs to improve animal growth performance. In this study, the genome of Lactobacillus salivarius NRRL B-30514, a BSH-producing strain isolated from chicken, was sequenced by a 454 GS FLX sequencer. A BSH gene identified by genome analysis was cloned and expressed in an Escherichia coli expression system for enzymatic analyses. The BSH displayed efficient hydrolysis activity for both glycoconjugated and tauroconjugated bile salts, with slightly higher catalytic efficiencies (k cat /K m ) on glycoconjugated bile salts. The optimal pH and temperature for the BSH activity were 5.5 and 41°C, respectively. Examination of a panel of dietary compounds using the purified BSH identified some potent BSH inhibitors, in which copper and zinc have been recently demonstrated to promote feed digestion and body weight gain in different food animals. In sum, this study identified and characterized a BSH with broad substrate specificity from a chicken L. salivarius strain and established a solid platform for us to discover novel BSH inhibitors, the promising feed additives to replace AGPs for enhancing the productivity and sustainability of food animals.

Lactobacillus gasseri in the Upper Small Intestine Impacts an ACSL3-Dependent Fatty Acid-Sensing Pathway Regulating Whole-Body Glucose Homeostasis

“…Transplantation of metformin-treated microbiota instead increases Lactobacillus salivarius in parallel to a restoration of an upper small intestinal SGLT1-dependent glucoregulatory glucose-sensing pathway (Bauer et al, 2018). Given that L. gasseri activates an ACSL3-dependent glucoregulatory lipid-sensing pathway via FXR inhibition in the upper small intestine ( Figure 7), and that L. salivarius, like L. gasseri, exhibits bile salt hydrolase activity (Wang et al, 2012;Xu et al, 2016), which could impact the bile acid pool and subsequent FXR activity, we propose (which clearly warrants future investigation) that upper small intestinal FXR could be a common pathway that links members of the Lactobacillus genus, such as L. gasseri and L. salivarius, with nutrient-sensing mechanisms to exert glucoregulatory effects in obesity and diabetes.…”

Bacterial bile salt hydrolase in host metabolism: Potential for influencing gastrointestinal microbe-host crosstalk

“…8,23,51,52 The work also supports the intriguing concept of specifically targeting intestinal bile salt hydrolase activity to enhance weight gain in animal husbandry. 23,24,53…”

Discovery of Bile Salt Hydrolase Inhibitors Using an Efficient High-Throughput Screening System

“…Expression of the His-tagged rBSH and purification by nickel-nitrilotriacetic acid (Ni 2+ -NTA) affinity chromatography was carried out as described in our previous publication [20], [30], [31].…”