Garibay Darline, Zaborska Karolina E, Shanahan Michael, Zheng Qiaonan, Kelly Katie M, Montrose David C, Dannenberg Andrew J, Miller Andrew D, Sethupathy Praveen, Cummings Bethany P
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, 10021, USA.
Obes Surg. 2019 May;29(5):1593-1601. doi: 10.1007/s11695-019-03707-9.
Bariatric surgery, such as vertical sleeve gastrectomy (VSG), is the most effective long-term treatment for obesity. However, there are conflicting reports on the effect of bariatric surgery on inflammatory bowel disease (IBD). Bariatric surgery increases bile acid concentrations, which can decrease inflammation by signaling through the bile acid receptor, TGR5. TGR5 signaling protects against chemically induced colitis in mice. VSG increases circulating bile acid concentrations to increase TGR5 signaling, which contributes to improved metabolic regulation after VSG. Therefore, we investigated the effect of VSG on chemically induced colitis development and the role of TGR5 in this context.
VSG or sham surgery was performed in high fat diet-fed male Tgr5 and Tgr5 littermates. Sham-operated mice were food restricted to match their body weight to VSG-operated mice. Colitis was induced with 2.5% dextran sodium sulfate (DSS) in water post-operatively. Body weight, energy intake, fecal scoring, colon histopathology, colonic markers of inflammation, goblet cell counts, and colonic microRNA-21 levels were assessed.
VSG decreased body weight independently of genotype. Consistent with previous work, genetic ablation of TGR5 increased the severity of DSS-induced colitis. Notably, despite the effect of VSG to decrease body weight and increase TGR5 signaling, VSG increased the severity of DSS-induced colitis. VSG-induced increases in colitis were associated with increased colonic expression of TNF-α, IL-6, MCP-1, and microRNA-21.
While our data demonstrate that TGR5 protects against colitis, they also demonstrate that VSG potentiates chemically induced colitis in mice. These data suggest that individuals undergoing VSG may be at increased risk for developing colitis; however, further study is needed.
减重手术，如垂直袖状胃切除术（VSG），是治疗肥胖最有效的长期方法。然而，关于减重手术对炎症性肠病（IBD）的影响，存在相互矛盾的报道。减重手术会增加胆汁酸浓度，胆汁酸可通过胆汁酸受体TGR5发出信号来减轻炎症。TGR5信号传导可保护小鼠免受化学诱导的结肠炎。VSG会增加循环胆汁酸浓度以增强TGR5信号传导，这有助于VSG术后改善代谢调节。因此，我们研究了VSG对化学诱导的结肠炎发展的影响以及TGR5在此过程中的作用。
对高脂饮食喂养的雄性Tgr5基因敲除小鼠及其同窝对照小鼠进行VSG或假手术。对接受假手术的小鼠进行食物限制，使其体重与接受VSG手术的小鼠相匹配。术后在水中用2.5%的葡聚糖硫酸钠（DSS）诱导结肠炎。评估体重、能量摄入、粪便评分、结肠组织病理学、结肠炎症标志物、杯状细胞计数以及结肠微小RNA-21水平。
VSG可独立于基因型减轻体重。与之前的研究一致，TGR5基因敲除会增加DSS诱导的结肠炎的严重程度。值得注意的是，尽管VSG有减轻体重和增强TGR5信号传导的作用，但它却增加了DSS诱导的结肠炎的严重程度。VSG诱导的结肠炎加重与结肠中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、单核细胞趋化蛋白-1（MCP-1）和微小RNA-21表达增加有关。
虽然我们的数据表明TGR5可预防结肠炎，但也表明VSG会增强化学诱导的小鼠结肠炎。这些数据表明，接受VSG手术的个体患结肠炎的风险可能增加；然而，还需要进一步研究。
