Evaluation of bile salt hydrolase inhibitor efficacy for modulating host bile profile and physiology using a chicken model system

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Date
2020-03-18
Authors
Geng, Wenjing
Long, Sarah L.
Chang, Yun-Juan
Saxton, Arnold M.
Joyce, Susan A.
Lin, Jun
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Publisher
Springer Nature
Published Version
10.1038/s41598-020-61723-7
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Abstract
Gut microbial enzymes, bile salt hydrolases (BSHs) are the gateway enzymes for bile acid (BA) modification in the gut. This activity is a promising target for developing innovative non-antibiotic growth promoters to enhance animal production and health. Compelling evidence has shown that inhibition of BSH activity should enhance weight gain by altering the BA pool, host signalling and lipid metabolism. We recently identified a panel of promising BSH inhibitors. Here, we address the potential of them as alternative, effective, non-antibiotic feed additives, for commercial application, to promote animal growth using a chicken model. In this study, the in vivo efficacy of three BSH inhibitors (caffeic acid phenethylester, riboflavin, carnosic acid) were evaluated. 7-day old chicks (10 birds/group) were either untreated or they received one of the specific BSH inhibitors (25 mg/kg body weight) via oral gavage for 17 days. The chicks in treatment groups consistently displayed higher body weight gain than the untreated chicks. Metabolomic analysis demonstrated that BSH inhibitor treatment led to significant changes in both circulating and intestinal BA signatures in support of blunted intestinal BSH activity. Consistent with this finding, liver and intestinal tissue RNA-Seq analysis showed that carnosic acid treatment significantly altered expression of genes involved in lipid and bile acid metabolism. Taken together, this study validates microbial BSH activity inhibition as an alternative target and strategy to antibiotic treatment for animal growth promotion.
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Keywords
Antibiotic growth promoters (AGPs) , Non-antibiotic feed additives , Gut microbial enzymes
Citation
Geng W., Long S. L., Chang Y. J., Saxton A. M., Joyce S. A. and Lin, J. (2020) 'Evaluation of bile salt hydrolase inhibitor efficacy for modulating host bile profile and physiology using a chicken model system', Scientific Reports, 10, 4941, (20 pp). doi: 10.1038/s41598-020-61723-7
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https://hdl.handle.net/10468/9818
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Biochemistry and Cell Biology - Journal Articles
APC Microbiome Ireland - Journal Articles
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© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.