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Deoxycholic Acid-Induced Gut Dysbiosis Disrupts Bile Acid Enterohepatic Circulation and Promotes Intestinal Inflammation

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Abstract

Background

A Western diet is a risk factor for the development of inflammatory bowel disease (IBD). High levels of fecal deoxycholic acid (DCA) in response to a Western diet contribute to bowel inflammatory injury. However, the mechanism of DCA in the natural course of IBD development remains unanswered.

Aims

The aim of this study is to investigate the effect of DCA on the induction of gut dysbiosis and its roles in the development of intestinal inflammation.

Methods

Wild-type C57BL/6J mice were fed an AIN-93G diet, either supplemented with or without 0.2% DCA, and killed at 24 weeks. Distal ileum and colon tissues were assessed by histopathological analysis. Hepatic and ileal gene expression was examined by qPCR, and the gut microbiota was analyzed by high-throughput 16S rRNA gene sequencing. HPLC–MS was used for fecal bile acid quantification.

Results

Mice fed the DCA-supplemented diet developed focal areas of ileal and colonic inflammation, accompanied by alteration of the composition of the intestinal microbiota and accumulation of fecal bile acids. DCA-induced dysbiosis decreased the deconjugation of bile acids, and this regulation was associated with the repressed expression of target genes in the enterohepatic farnesoid X receptor–fibroblast growth factor (FXR–FGF15) axis, leading to upregulation of hepatic de novo bile acid synthesis.

Conclusions

These results suggest that DCA-induced gut dysbiosis may act as a key etiologic factor in intestinal inflammation, associated with bile acid metabolic disturbance and downregulation of the FXR–FGF15 axis.

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Acknowledgments

This study is supported by the Grant (81700456 to M.Q.X) from the National Natural Science Foundation of China and the Grant (2018KY104 to M.Q.X) from the Medical Health Technology Project of Zhejiang, China.

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Author notes

  1. Mengque Xu and Mengsha Cen have contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China

    Mengque Xu, Mengsha Cen, Yuqin Shen, Yubin Zhu, Fangli Cheng, Linlin Tang, Weiling Hu & Ning Dai

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  1. Mengque Xu
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  2. Mengsha Cen
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  8. Ning Dai
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Contributions

Mengque Xu took part in conceptualization; Mengsha Cen and Yubin Zhu involved in data curation; Mengque Xu, Mengsha Cen, and Yuqin Shen took part in formal analysis; Mengque Xu participated in funding acquisition; Mengsha Cen, Yuqin Shen, Fangli Chen, and Weiling Hu involved in investigation; Mengsha Cen, Yuqin Shen, Yubin Zhu, Fangli Chen, and Weiling Hu took part in methodology; Mengque Xu and Ning Dai contributed to project administration; Mengque Xu involved in writing—original draft; Mengque Xu, Linlin Tang, and Ning Dai participated in writing—review and editing.

Corresponding author

Correspondence to Ning Dai.

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The authors have no conflict of interest.

Ethics approval

This study was conducted with the approval of Institutional Animal Care and Use Committee at Zhejiang Chinese Medical University, Zhejiang, P. R. China.

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Xu, M., Cen, M., Shen, Y. et al. Deoxycholic Acid-Induced Gut Dysbiosis Disrupts Bile Acid Enterohepatic Circulation and Promotes Intestinal Inflammation. Dig Dis Sci 66, 568–576 (2021). https://doi.org/10.1007/s10620-020-06208-3

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  • DOI: https://doi.org/10.1007/s10620-020-06208-3

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