Simulating the Post-gastric Bypass Intestinal Microenvironment Uncovers a Barrier-Stabilizing Role for FXR

被引：6

作者：

Hankir, Mohammed K. ^{[1
]}

Langseder, Theresa ^{[1
]}

Bankoglu, Ezgi Eyluel ^{[2
]}

Ghoreishi, Yalda ^{[1
]}

Dischinger, Ulrich ^{[3
]}

Kurlbaum, Max ^{[3
]}

Kroiss, Matthias ^{[3
]}

Otto, Christoph ^{[1
]}

le Roux, Carel W. ^{[4
]}

Arora, Tulika ^{[5
]}

Seyfried, Florian ^{[1
]}

Schlegel, Nicolas ^{[1
]}

机构：

[1] Univ Hosp Wuerzburg, Ctr Operat Med, Dept Gen Visceral Transplant Vasc & Pediat Surg, Oberduerrbacherstr 6, D-97080 Wurzburg, Bavaria, Germany

[2] Univ Wurzburg, Inst Pharmacol & Toxicol, D-97080 Wurzburg, Bavaria, Germany

[3] Univ Hosp Wuerzburg, Dept Endocrinol & Diabetol, D-97080 Wurzburg, Bavaria, Germany

[4] Univ Coll Dublin, Diabet Complicat Res Ctr, Dublin 4, Ireland

[5] Univ Copenhagen, Novo Nordisk Fdn, Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark

来源：

ISCIENCE | 2020年 / 23卷 / 12期

关键词：

PERIPHERAL INSULIN SENSITIVITY; VERTICAL SLEEVE GASTRECTOMY; GLYCEMIC CONTROL; WEIGHT-LOSS; METABOLIC ENDOTOXEMIA; BARIATRIC SURGERY; BILE-ACIDS; CALORIE RESTRICTION; GLUCOSE-HOMEOSTASIS; DIABETES REMISSION;

D O I：

10.1016/j.isci.2020.101777

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Regional 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-freemice 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.

引用

页数：31