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

Area of Science:

• Gastroenterology
• Immunology
• Endocrinology

Background:

• Bariatric surgery, like vertical sleeve gastrectomy (VSG), is effective for obesity but its impact on inflammatory bowel disease (IBD) is debated.
• Increased bile acid concentrations post-bariatric surgery may reduce inflammation via TGR5 signaling, a pathway known to protect against colitis in mice.
• VSG elevates circulating bile acids, enhancing TGR5 signaling and improving metabolic regulation.

Purpose of the Study:

• To investigate the effect of VSG on chemically induced colitis development in mice.
• To determine the role of TGR5 signaling in the context of VSG and colitis.

Main Methods:

• VSG or sham surgery was performed on mice on a high-fat diet, with TGR5 intact (Tgr5^+/+) or ablated (Tgr5^-/-).
• Colitis was induced using dextran sodium sulfate (DSS).
• Outcomes assessed included body weight, energy intake, fecal scores, colon histopathology, inflammatory markers, goblet cell counts, and microRNA-21 levels.

Main Results:

• VSG reduced body weight irrespective of TGR5 genotype.
• TGR5 deficiency exacerbated DSS-induced colitis, confirming its protective role.
• VSG significantly increased the severity of DSS-induced colitis, associated with elevated colonic TNF-α, IL-6, MCP-1, and microRNA-21.

Conclusions:

• TGR5 signaling is protective against colitis.
• VSG potentiates chemically induced colitis in mice, indicating a potential increased risk for colitis in patients undergoing this procedure.
• Further research is necessary to fully understand the implications of VSG on colitis development.