Leaky Gut as a Potential Culprit for the Paradoxical Dysglycemic Response to Gastric Bypass-Associated Ileal Microbiota

• Main Authors: Mohammed K. Hankir, Florian Seyfried, Isabel N. Schellinger, Nicolas Schlegel, Tulika Arora
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Metabolites
• Subjects: Roux-en-Y gastric bypass surgery; intestinal microbiota; intestinal epithelial barrier; systemic endotoxemia; Type 2 diabetes
• Online Access: https://www.mdpi.com/2218-1989/11/3/153

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.