TGR5 Protects Against Colitis in Mice, but Vertical Sleeve Gastrectomy Increases Colitis Severity.

Abstract:

BACKGROUND AND AIMS: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

journal_name

Obes Surg

journal_title

Obesity surgery

authors

Garibay D,Zaborska KE,Shanahan M,Zheng Q,Kelly KM,Montrose DC,Dannenberg AJ,Miller AD,Sethupathy P,Cummings BP

doi

10.1007/s11695-019-03707-9

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

1593-1601

issue

5

eissn

0960-8923

issn

1708-0428

pii

10.1007/s11695-019-03707-9

journal_volume

29

pub_type

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