Deoxycholic Acid-Induced Gut Dysbiosis Disrupts Bile Acid Enterohepatic Circulation and Promotes Intestinal Inflammation
Deoxycholic Acid-Induced Gut Dysbiosis Disrupts Bile Acid Enterohepatic Circulation and Promotes Intestinal Inflammation
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脱氧胆酸引起的肠道菌群失调会扰乱胆汁酸肠肝循环并促进肠道炎症
DOI：
10.1007/s10620-020-06208-3
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Ning Dai
中科院分区：
文献类型：
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作者：
Mengque Xu;Mengsha Cen;Yuqin Shen;Yubin Zhu;Fangli Cheng;Linlin Tang;Weiling Hu;Ning Dai
背景西方饮食是炎症性肠病（IBD）发生的危险因素。西方饮食导致粪便中高水平的脱氧胆酸 (DCA) 会导致肠道炎症损伤。然而，DCA 在 IBD 发展自然过程中的机制仍未得到解答。目的本研究的目的是研究 DCA 对诱导肠道菌群失调的影响及其在肠道炎症发展中的作用。方法将野生型 C57BL/6J 小鼠饲喂 AIN-93G 饮食，添加或不添加 0.2% DCA，并在 24 周时处死。通过组织病理学分析评估远端回肠和结肠组织。通过 qPCR 检查肝脏和回肠基因表达，并通过高通量 16S rRNA 基因测序分析肠道微生物群。 HPLC-MS 用于粪便胆汁酸定量。结果喂食添加 DCA 的饮食的小鼠出现了回肠和结肠炎症的局部区域，伴随着肠道微生物群组成的改变和粪便胆汁酸的积累。 DCA诱导的肠道菌群失调减少了胆汁酸的去结合，这种调节与肠肝法尼醇X受体-成纤维细胞生长因子（FXR-FGF15）轴中靶基因的抑制表达有关，导致肝脏胆汁酸从头合成上调。结论这些结果表明，DCA诱导的肠道菌群失调可能是肠道炎症的关键病因，与胆汁酸代谢紊乱和胆汁酸代谢下调相关。 FXR–FGF15 轴。
BackgroundA 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.AimsThe 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.MethodsWild-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.ResultsMice 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.ConclusionsThese 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.