APM OpenIR
Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation
Tian, Yuan1,2; Cai, Jingwei1; Gui, Wei1; Nichols, Robert G.1; Koo, Imhoi1; Zhang, Jingtao1; Anitha, Mallappa1; Patterson, Andrew D.1
2019-02-01
Source PublicationDRUG METABOLISM AND DISPOSITION
ISSN0090-9556
Volume47Issue:2Pages:86-93
AbstractIntestinal bacteria play an important role in bile acid metabolism and in the regulation of multiple host metabolic pathways (e.g., lipid and glucose homeostasis) through modulation of intestinal farnesoid X receptor (FXR) activity. Here, we examined the effect of berberine (BBR), a natural plant alkaloid, on intestinal bacteria using in vitro and in vivo models. In vivo, the metabolomic response and changes in mouse intestinal bacterial communities treated with BBR (100 mg/kg) for 5 days were assessed using NMR- and mass spectrometry-based metabolomics coupled with multivariate data analysis. Short-term BBR exposure altered intestinal bacteria by reducing Clostridium cluster XIVa and IV and their bile salt hydrolase (BSH) activity, which resulted in the accumulation of taurocholic acid (TCA). The accumulation of TCA was associated with activation of intestinal FXR, which can mediate bile acid, lipid, and glucose metabolism. In vitro, isolated mouse cecal bacteria were incubated with three doses of BBR (0.1, 1, and 10 mg/ml) for 4 hours in an anaerobic chamber. NMR-based metabolomics combined with flow cytometry was used to evaluate the direct physiologic and metabolic effect of BBR on the bacteria. In vitro, BBR exposure not only altered bacterial physiology but also changed bacterial community composition and function, especially reducing BSH-expressing bacteria like Clostridium spp. These data suggest that BBR directly affects bacteria to alter bile acid metabolism and activate FXR signaling. These data provide new insights into the link between intestinal bacteria, nuclear receptor signaling, and xenobiotics.
Funding OrganizationPennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; National Institutes of Health National Library of Medicine ; National Institutes of Health National Library of Medicine ; U.S. Department of Agriculture National Institute of Food and Agriculture ; U.S. Department of Agriculture National Institute of Food and Agriculture ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; National Institutes of Health National Library of Medicine ; National Institutes of Health National Library of Medicine ; U.S. Department of Agriculture National Institute of Food and Agriculture ; U.S. Department of Agriculture National Institute of Food and Agriculture ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; National Institutes of Health National Library of Medicine ; National Institutes of Health National Library of Medicine ; U.S. Department of Agriculture National Institute of Food and Agriculture ; U.S. Department of Agriculture National Institute of Food and Agriculture ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; National Institutes of Health National Library of Medicine ; National Institutes of Health National Library of Medicine ; U.S. Department of Agriculture National Institute of Food and Agriculture ; U.S. Department of Agriculture National Institute of Food and Agriculture
DOI10.1124/dmd.118.083691
WOS KeywordBILE-ACID METABOLISM ; NUCLEAR RECEPTOR ; SALT HYDROLASE ; EXPRESSION ; HOST ; MECHANISM ; MICE ; DIET
Language英语
Funding ProjectPennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; National Institutes of Health National Library of Medicine[T32LM12415-1] ; U.S. Department of Agriculture National Institute of Food and Agriculture[2914-38420-21822]
Funding OrganizationPennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; National Institutes of Health National Library of Medicine ; National Institutes of Health National Library of Medicine ; U.S. Department of Agriculture National Institute of Food and Agriculture ; U.S. Department of Agriculture National Institute of Food and Agriculture ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; National Institutes of Health National Library of Medicine ; National Institutes of Health National Library of Medicine ; U.S. Department of Agriculture National Institute of Food and Agriculture ; U.S. Department of Agriculture National Institute of Food and Agriculture ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; National Institutes of Health National Library of Medicine ; National Institutes of Health National Library of Medicine ; U.S. Department of Agriculture National Institute of Food and Agriculture ; U.S. Department of Agriculture National Institute of Food and Agriculture ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; Pennsylvania Department of Health [Tobacco Commonwealth Universal Research Enhancement Funds] ; National Institutes of Health National Library of Medicine ; National Institutes of Health National Library of Medicine ; U.S. Department of Agriculture National Institute of Food and Agriculture ; U.S. Department of Agriculture National Institute of Food and Agriculture
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000457846400004
PublisherAMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
Citation statistics
Cited Times:13[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.apm.ac.cn/handle/112942/14320
Collection中国科学院武汉物理与数学研究所
Corresponding AuthorPatterson, Andrew D.
Affiliation1.Penn State Univ, Dept Vet & Biomed Sci, 322 Life Sci Bldg, University Pk, PA 16802 USA
2.Univ Chinese Acad Sci, Natl Ctr Magnet Resonance Wuhan, Key Lab Magnet Resonance Biol Syst,Chinese Acad S, Wuhan Inst Phys & Math,State Key Lab Magnet Res &, Wuhan, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Tian, Yuan,Cai, Jingwei,Gui, Wei,et al. Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation[J]. DRUG METABOLISM AND DISPOSITION,2019,47(2):86-93.
APA Tian, Yuan.,Cai, Jingwei.,Gui, Wei.,Nichols, Robert G..,Koo, Imhoi.,...&Patterson, Andrew D..(2019).Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation.DRUG METABOLISM AND DISPOSITION,47(2),86-93.
MLA Tian, Yuan,et al."Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation".DRUG METABOLISM AND DISPOSITION 47.2(2019):86-93.
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