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

  • Darline Garibay
  • Karolina E. Zaborska
  • Michael Shanahan
  • Qiaonan Zheng
  • Katie M. Kelly
  • David C. Montrose
  • Andrew J. Dannenberg
  • Andrew D. Miller
  • Praveen Sethupathy
  • Bethany P. CummingsEmail author
Original Contributions
  • 83 Downloads

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.

Keywords

VSG Colitis TGR5 

Notes

Acknowledgements

We thank the Animal Health and Diagnostic Center Histopathology Core and Martin Slade for preparation of samples for H&E.

Funding

This research was supported by NIH grant R21CA195002.

Compliance with Ethical Standards

The experimental protocols were approved by the Cornell University Institutional Animal Care and Use Committee.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All experimental protocols were approved by the Cornell University Institutional Animal Care and Use Committee, and all applicable institutional and/or national guidelines for the care and use of animals were followed.

Informed Consent

Does not apply.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Darline Garibay
    • 1
  • Karolina E. Zaborska
    • 1
  • Michael Shanahan
    • 1
  • Qiaonan Zheng
    • 1
  • Katie M. Kelly
    • 1
  • David C. Montrose
    • 2
  • Andrew J. Dannenberg
    • 2
  • Andrew D. Miller
    • 1
  • Praveen Sethupathy
    • 1
  • Bethany P. Cummings
    • 1
    Email author
  1. 1.Department of Biomedical Sciences, College of Veterinary MedicineCornell UniversityIthacaUSA
  2. 2.Department of MedicineWeill Cornell Medical CollegeNew YorkUSA

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