Obese mice exhibit more severe inflammatory colitis following sleeve gastrectomy
*James N Luo, *Renuka Subramaniam, *Hassan Aliabarian, *Tammy Lo, *Tiegang Liu, Ali Tavakkoli, James Yoo, Eric Sheu
Brigham and Women's Hospital, Boston, MA
Objective: The biological effects of obesity and bariatric surgery on inflammatory bowel disease remain elusive. Here, we aim to evaluate the effect of sleeve gastrectomy on the development of inflammatory colitis. Design: Weight matched diet-induced obese (DIO) mice were randomized to undergo either sleeve gastrectomy (n=15) or sham surgery (n=17). 3 weeks following surgery, mice were administered 2.5% of Dextran Sodium Sulfate (DSS) via drinking water for 7 days. Setting: Approved by the Institutional Animal Care and Use Committee at the Brigham and Women’s Hospital.
Patients: 11 weeks-old male DIO mice on the C57BL/6J background underwent randomization and were maintained on a high fat diet (60% fat) for the entire study. Interventions: Sleeve gastrectomy (SG) or sham (laparotomy with short gastric arteries ligation). Main Outcome Measures: Colitis severity was assessed by tracking weight, stool consistency, and hematochezia, which were used to calculate the Disease Activity Index (DAI). Weight change following surgery was also measured. Results: SG mice exhibited significantly greater weight loss compared to sham mice (Figure 1A, p<0.001). SG mice exhibited significantly worse hematochezia and diarrhea, as well as higher overall DAI than sham with DSS administration (p<0.001), reflecting a more severe colitis phenotype (Figure 1B).
Conclusions: DIO mice undergoing SG had significantly greater weight loss and exhibited more severe colitis following DSS administration. These observations demonstrate the mechanistic utility of this preclinical model, and highlight the importance of further clinical investigation into the effects of bariatric surgery on inflammatory bowel disease.
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