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-free mice in association with suppression of endotoxemia. Correspondingly, they had direct barrier-stabilizing effects on an intestinal epithelial cell line which, 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.

Roux-en-Y 胃绕道手术 (RYGB) 手术带来的肠道微环境的区域性变化可能通过有利地调节各种局部细胞过程而有助于其一些有效的全身代谢益处。在这里，我们发现，与假手术大鼠相比，RYGB 手术大鼠的肠道内容物区域依赖性地赋予受体无菌小鼠更好的血糖控制，并与内毒素血症的抑制相关。相应地，它们对肠上皮细胞系具有直接的屏障稳定作用，该细胞系暴露于胆汁的肠内容物部分依赖于法尼醇X受体（FXR）。此外，循环成纤维细胞生长因子 19 水平（肠道 FXR 激活的读数）与 RYGB 患者纵向队列中的内毒素血症严重程度呈负相关。这些发现表明，各种宿主和/或微生物群衍生的管腔因子通过 FXR 信号传导，区域特异性地协同稳定 RYGB 后的肠上皮屏障，这可能有助于更好地治疗非肥胖症中内毒素血症诱导的胰岛素抵抗。侵入性和更有针对性的方式。