TY - JOUR A1 - Hankir, Mohammed K. A1 - Seyfried, Florian A1 - Schellinger, Isabel N. A1 - Schlegel, Nicolas A1 - Arora, Tulika T1 - Leaky gut as a potential culprit for the paradoxical dysglycemic response to gastric bypass-associated ileal microbiota JF - Metabolites N2 - Altered host-intestinal microbiota interactions are increasingly implicated in the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. We previously found, however, that RYGB-associated ileal microbiota can paradoxically impair host glycemic control when transferred to germ-free mice. Here we present complementary evidence suggesting that this could be due to the heightened development of systemic endotoxemia. Consistently, application of ileal content from RYGB-treated compared with sham-operated rats onto Caco-2 cell monolayers compromised barrier function and decreased expression of the barrier-stabilizing proteins claudin-4 and desmoglein-2. Our findings raise the possibility that RYGB-associated ileal microbiota produce and release soluble metabolites which locally increase intestinal permeability to promote systemic endotoxemia-induced insulin resistance, with potential implications for the treatment of RYGB patients who eventually relapse onto type 2 diabetes. KW - Roux-en-Y gastric bypass surgery KW - intestinal microbiota KW - intestinal epithelial barrier KW - systemic endotoxemia KW - type 2 diabetes Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234085 SN - 2218-1989 VL - 11 IS - 3 ER -