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

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dc.contributor.authorGeng, Wenjing
dc.contributor.authorLong, Sarah L.
dc.contributor.authorChang, Yun-Juan
dc.contributor.authorSaxton, Arnold M.
dc.contributor.authorJoyce, Susan A.
dc.contributor.authorLin, Jun
dc.contributor.funderUniversity of Tennesseeen
dc.contributor.funderU.S. Department of Agricultureen
dc.contributor.funderNational Institute of Food and Agricultureen
dc.contributor.funderDepartment of Agriculture, Food and the Marine, Irelanden
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderEuropean Commissionen
dc.date.accessioned2020-04-08T09:18:09Z
dc.date.available2020-04-08T09:18:09Z
dc.date.issued2020-03-18
dc.date.updated2020-04-06T16:51:34Z
dc.description.abstractGut 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.en
dc.description.sponsorshipThe University of Tennessee AgResearch and United States Department of Agriculture National Institute of Food and Agriculture ((NIFA) Award No. 2018-67015-27475)); Department of Agriculture, Food and the Marine Ireland ((DAFM) Award No. DAFM 17-RD-US-ROI); Science Foundation of Ireland and European Commission (SFI-EU JPI CABALA (Grant Number 16/ERA-HDHL/3358))en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationGeng 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/s41598-020-61723-7en
dc.identifier.doi10.1038/s41598-020-61723-7en
dc.identifier.endpage4941en
dc.identifier.issn2045-2322
dc.identifier.issued1en
dc.identifier.journaltitleScientific Reportsen
dc.identifier.startpage20en
dc.identifier.urihttps://hdl.handle.net/10468/9818
dc.identifier.volume10en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.rights© 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/.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/.en
dc.subjectAntibiotic growth promoters (AGPs)en
dc.subjectNon-antibiotic feed additivesen
dc.subjectGut microbial enzymesen
dc.titleEvaluation of bile salt hydrolase inhibitor efficacy for modulating host bile profile and physiology using a chicken model systemen
dc.typeArticle (peer-reviewed)en
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