Building and breaking the gut barrier with bariatric surgery

Abstract

Bariatric surgery has been proposed to improve glycemic control in morbidly obese patients by stabilising the gut barrier and alleviating endotoxemia-induced insulin resistance. Here, recent studies are highlighted which reveal site-specific and at times opposing effects of bariatric surgery on the gut barrier. Further understanding the underlying mechanisms may not only inform the development of novel gut-based drugs for the initial treatment of type 2 diabetes, but possibly also assist in the management of its eventual relapse.

Novel Insights into the Physiology of Nutrient Sensing and Gut-Brain Communication in Surgical and Experimental Obesity Therapy

“…On the other hand, transplanting colonic microbiota of RYGB-operated rats to germ-free mice improved oral glucose tolerance, possibly by stabilizing the intestinal epithelial barrier through increased bile acid receptor FXR signaling via the generation of secondary bile acids [39]. These findings suggest that the changes in gut microbiota and their associated metabolites after RYGB may have opposing effects on glycemic control, depending on the gut region [40]. For SG, cecal and fecal levels of the primary bile acid cholic acid-7 sulfate (CA7S) have been found to increase in mice and patients after surgery [41].…”

“…In mice treated with GDF15, there was a reduced preference for a high-fat diet [114]. Notably, RYGB-operated rats have increased circulating and portal vein GDF15 levels, and this is negatively correlated with their food intake and body weight [40]. While a separate study also showed increased circulating GDF15 levels and GDF15 protein in the gastric pouch, jejunum, and ileum of RYGB-operated rats [115], more data is needed to establish a causal link between gutderived GDF15 and the beneficial effects of BS [116,117].…”