RYGB and SG Induce Conserved Small Intestinal Cytokine Signatures Associated with Diabetes
Renuka Subramaniam DVM,PhD, Hina Y Bhutta MD, Hassan Aliakbarian MD, Eleanor Rudge MD, David Harris MD, Ali Tavakkoli MD, Eric G Sheu MD, PhD
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Background: Dysregulation of intestinal immune defenses in diabetes leads to systemic inflammation and, consequently, insulin resistance. Roux-en-Y gastric bypass (RYGB) and, sleeve gastrectomy (SG) induce type 2 diabetes (T2D) remission. We hypothesize that bariatric surgery triggers changes in intestinal mucosal immunity that contribute to T2D resolution.
Methods: RYGB, SG, and sham-operations were performed in SD rats (n=5-6 / group). RNA was isolated from mucosal scrapings of the Roux (Rx) and biliopancreatic (BP) limbs, or equivalent intestinal segments, at 4 weeks post-operatively. Key cytokines involved in insulin resistance (TNFα, IFNγ), inflammasome activation (IL-1beta, IL-18), resolution of inflammation (IL-10, IL-33), and innate lymphoid and Th17 cell responses (IL-17, IL-23) were measured by qPCR.
Results: After RYGB, cytokine expression was markedly changed in the Rx limb but not the BP limb (Table 1). Levels of pro-inflammatory and Th17 cytokines including TNFα, IFNγ, IL-17, IL-23, and IL-18 were significantly reduced in Rx limb after RYGB compared to controls (p<0.01). In tandem, 3-4 fold increases of the pro-resolution cytokines IL-10 (p<0.08) and IL-33 (p<0.02) were observed. Interestingly, significant small intestinal changes in cytokine profile were also seen after SG. However, unlike the RYGB, SG downregulated IL-33 expression (p < 0.03) and increased IL-18 expression p < 0.01).
Conclusions: RYGB and SG induce remarkably similar, segment specific, small intestinal cytokine signatures associated with resolution of mucosal inflammation. Given the unique impact of RYGB on IL-33 may be of interest to understand the superior anti-diabetic effects of RYGB. 
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