Roux‐en‐Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats

Abstract

Background Postoperative modulation of the gut microbiome has been suggested to contribute to the metabolic benefits after metabolic surgery, but the mechanisms underlying these metabolic benefits remain unknown. Previously, we reported that Roux‐en‐Y gastric bypass (RYGB) surgery in Zucker diabetic fatty (ZDF) rats increased the abundance of Proteobacteria and Gammaproteobacteria. However, theoretically, these Gram‐negative bacteria may elevate lipopolysaccharide (LPS) levels. Therefore, in this study we further investigated the potential mechanisms by which RYGB improves glucose homeostasis, endotoxemia, and inflammatory stress in ZDF rats. Methods Rats were divided into three groups: (a) an RYGB group (RY); (b) a sham‐operated group pair‐fed with the RY group; and (c) a sham‐operated group fed ad libitum. Changes in LPS, cytokine levels, intestinal permeability (evaluated using the fluorescein isothiocyanate‐dextran method), and intestinal epithelial tight junction proteins zona occludins (ZO)‐1, occludin, and claudin‐1 were assessed 10 weeks postoperatively. Results Rats that underwent RYGB exhibited sustained weight loss and reduced glucose, as well as lower cytokine and LPS concentrations, than rats in the control groups. In the colonic epithelium, ZO1 and claudin‐1 (Cldn1) mRNA levels were higher in the RY than control groups. Intestinal permeability declined in the RY group and was positively correlated with LPS levels and negatively correlated with ZO‐1, occludin, and claudin‐1 expression. Conclusions The results demonstrate that RYGB can reduce the extent of endotoxemia and inflammation, which is associated with improved tight junction integrity and intestinal barrier strength. These effects may explain why a low level of inflammation is maintained after RYGB and the postoperative increase in Gram‐negative bacteria.

Roux-En-Y Gastric Bypass Improved Intestinal Permeability by Regulating Gut Innate Immunity in Diet-Induced Obese Mice

“…As chronic in ammation has been proven to play an essential role in insulin resistance and metabolic syndrome 19,20 , we measured in ammatory cytokines in peripheral blood which concluded that RYGB substantially reduced systemic in ammation, as supported by the nding that IL6 and TNFα were decreased in the RYGB group. Moreover, our study found that serum LPS levels were signi cantly lower in the RYGB group than in the sham group, suggesting that the intestine became less permeable to gut-derived toxins, which is consistent with the ndings of relieved endotoxemia after RYGB in human studies [21][22][23] .…”

Gut Microbiota Dysbiosis in Human Obesity: Impact of Bariatric Surgery

“…This rather suggests that BS might be associated with decreased LPS translocation within the intestine into the systemic circulation, via a potential decreased intestinal permeability post-BS. Murine data have observed that RYGB improves tight-junction integrity and in-vivo intestinal permeability while reducing metabolic endotoxemia and systemic inflammation 64 . Yet, such observations in mice following BS remain to be confirmed in humans.…”

Impact of bariatric surgery on type 2 diabetes: contribution of inflammation and gut microbiome?

“…Literature has repeatedly reported the decrease of systemic LPS post-BS [151][152][153][154][155] , which has even been associated with improvements in insulin resistance and glucose control 152,154 . A recent murine study demonstrated that RYGB induced the improvement of tight-junction integrity and improved in-vivo intestinal permeability together with the reduction of metabolic endotoxemia and systemic inflammation 156 . This improved intestinal permeability could originate from 1) the observed reduction of fat intake post-BS 157 as fat intake indeed alters the gut barrier 27,30 or 2) the increased Akkermansia muciniphila observed post-BS.…”