Roux-en-Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats
RYGB手术减少内毒素血症和炎症应激反应同时改善肥胖糖尿病大鼠肠道通透性
Abstract
enBackground
Postoperative modulation of the gut microbiome has been suggested to contribute to the metabolic benefits after metabolic surgery, but the mechanisms underlying these metabolic benefits remain unknown. Previously, we reported that Roux-en-Y gastric bypass (RYGB) surgery in Zucker diabetic fatty (ZDF) rats increased the abundance of Proteobacteria and Gammaproteobacteria. However, theoretically, these Gram-negative bacteria may elevate lipopolysaccharide (LPS) levels. Therefore, in this study we further investigated the potential mechanisms by which RYGB improves glucose homeostasis, endotoxemia, and inflammatory stress in ZDF rats.
Methods
Rats were divided into three groups: (a) an RYGB group (RY); (b) a sham-operated group pair-fed with the RY group; and (c) a sham-operated group fed ad libitum. Changes in LPS, cytokine levels, intestinal permeability (evaluated using the fluorescein isothiocyanate-dextran method), and intestinal epithelial tight junction proteins zona occludins (ZO)-1, occludin, and claudin-1 were assessed 10 weeks postoperatively.
Results
Rats that underwent RYGB exhibited sustained weight loss and reduced glucose, as well as lower cytokine and LPS concentrations, than rats in the control groups. In the colonic epithelium, ZO1 and claudin-1 (Cldn1) mRNA levels were higher in the RY than control groups. Intestinal permeability declined in the RY group and was positively correlated with LPS levels and negatively correlated with ZO-1, occludin, and claudin-1 expression.
Conclusions
The results demonstrate that RYGB can reduce the extent of endotoxemia and inflammation, which is associated with improved tight junction integrity and intestinal barrier strength. These effects may explain why a low level of inflammation is maintained after RYGB and the postoperative increase in Gram-negative bacteria.
Abstract
zh摘要
背景
有研究表明代谢手术后肠道菌群的调节对于代谢获益具有关键作用，然而具体作用机制仍不明确。我们之前的研究表明，胃旁路术(Roux-en-Y gastric bypass, RYGB)手术后Zuker肥胖糖尿病大鼠(ZDF)的变形杆菌门和伽马变形杆菌纲均有显著增加，然而，理论上这些革兰氏阴性菌有可能提高体内脂多糖含量。因此，我们拟在ZDF大鼠模型上进一步探究RYGB改善血糖稳态、内毒素血症以及炎症应激反应的具体机制。
方法
我们将ZDF大鼠分为三组:(a) RYGB手术组(RY)，(b) 假手术但与RY组相同饮食组, (c) 假手术自由进食组，并测定三组大鼠术后10周的脂多糖、炎性细胞因子、肠道通透性变化(用测定荧光素-葡聚糖的方法)，以及肠道上皮紧密连接蛋白ZO-1、occludin以及claudin-1的表达水平并行相关分析。
结果
ZDF大鼠接收RYGB术后10周内体重持续减轻，血糖水平稳定下降，炎性细胞因子和脂多糖水平也比对照组更低。RY组大鼠肠道上皮的ZO-1和claudin-1的mRNA水平也比对照组更高。RY组大鼠肠道通透性降低并和脂多糖水平正相关，和ZO-1、occludin以及claudin-1的表达水平负相关。
结论
RYGB能够增强肠道上皮紧密连接的完整性，改善肠道通透性，从而有效抑制内毒素血症和炎症反应。这也一定程度解释了RYGB术后伴随革兰氏阴性菌的增加而炎症却维持在低水平，可能是RYGB改善代谢紊乱的机制之一。
