文章基本信息

标题：Simulating the Post-gastric Bypass Intestinal Microenvironment Uncovers a Barrier-Stabilizing Role for FXR
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作者：Mohammed K. Hankir ; Theresa Langseder ; Ezgi Eyluel Bankoglu 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：12
页码：1-32
DOI：10.1016/j.isci.2020.101777
语种：English
出版社：Elsevier
摘要：SummaryRegional changes to the intestinal microenvironment brought about by Roux-en-Y gastric bypass (RYGB) surgery may contribute to some of its potent systemic metabolic benefits through favorably regulating various local cellular processes. Here, we show that the intestinal contents of RYGB-operated compared with sham-operated rats region-dependently confer superior glycemic control to recipient germ-free mice in association with suppression of endotoxemia. Correspondingly, they had direct barrier-stabilizing effects on an intestinal epithelial cell line which, for bile-exposed intestinal contents, were partly farnesoid X receptor (FXR)-dependent. Further, circulating fibroblast growth factor 19 levels, a readout of intestinal FXR activation, negatively correlated with endotoxemia severity in longitudinal cohort of RYGB patients. These findings suggest that various host- and/or microbiota-derived luminal factors region-specifically and synergistically stabilize the intestinal epithelial barrier following RYGB through FXR signaling, which could potentially be leveraged to better treat endotoxemia-induced insulin resistance in obesity in a non-invasive and more targeted manner.Graphical AbstractDisplay OmittedHighlights•RYGB intestinal contents improve glycemia and suppress endotoxemia in GF mice•RYGB intestinal contents stabilize barrier function and structure in Caco-2 cells•This is partly FXR-dependent for bile-exposed intestinal contents only•Plasma bile acids and FGF19 negatively correlate with endotoxemia in RYGB patientsHuman Metabolism; Molecular Biology; Cell Biology