Simulating the Post-gastric Bypass Intestinal Microenvironment Uncovers a Barrier-Stabilizing Role for FXR
| Autor: | Max Kurlbaum, Nicolas Schlegel, Christoph Otto, Carel W. le Roux, Ezgi Eyluel Bankoglu, Florian Seyfried, Ulrich Dischinger, Theresa Langseder, Yalda Ghoreishi, Tulika Arora, Matthias Kroiss, Mohammed K. Hankir |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Gastric bypass 02 engineering and technology Fibroblast growth factor Human Metabolism Article 03 medical and health sciences Insulin resistance medicine Longitudinal cohort lcsh:Science Molecular Biology Intestinal contents Epithelial barrier Multidisciplinary business.industry nutritional and metabolic diseases Cell Biology 021001 nanoscience & nanotechnology medicine.disease Epithelium 030104 developmental biology medicine.anatomical_structure Cancer research Farnesoid X receptor lcsh:Q 0210 nano-technology business |
| Zdroj: | iScience iScience, Vol 23, Iss 12, Pp 101777-(2020) Hankir, M K, Langseder, T, Bankoglu, E E, Ghoreishi, Y, Dischinger, U, Kurlbaum, M, Kroiss, M, Otto, C, le Roux, C W, Arora, T, Seyfried, F & Schlegel, N 2020, ' Simulating the Post-gastric Bypass Intestinal Microenvironment Uncovers a Barrier-Stabilizing Role for FXR ', iScience, vol. 23, no. 12, 101777 . https://doi.org/10.1016/j.isci.2020.101777 |
| ISSN: | 2589-0042 |
| Popis: | Summary Regional changes to the intestinal microenvironment brought about by Roux-en-Y gastric bypass (RYGB) surgery may contribute to some of its potent systemic metabolic benefits through favorably regulating various local cellular processes. Here, we show that the intestinal contents of RYGB-operated compared with sham-operated rats region-dependently confer superior glycemic control to recipient germ-free mice in association with suppression of endotoxemia. Correspondingly, they had direct barrier-stabilizing effects on an intestinal epithelial cell line which, bile-exposed intestinal contents, were partly farnesoid X receptor (FXR)-dependent. Further, circulating fibroblast growth factor 19 levels, a readout of intestinal FXR activation, negatively correlated with endotoxemia severity in longitudinal cohort of RYGB patients. These findings suggest that various host- and/or microbiota-derived luminal factors region-specifically and synergistically stabilize the intestinal epithelial barrier following RYGB through FXR signaling, which could potentially be leveraged to better treat endotoxemia-induced insulin resistance in obesity in a non-invasive and more targeted manner. Graphical Abstract Highlights • RYGB intestinal contents improve glycemia and suppress endotoxemia in GF mice • RYGB intestinal contents stabilize barrier function and structure in Caco-2 cells • This is partly FXR-dependent for bile-exposed intestinal contents only • Plasma bile acids and FGF19 negatively correlate with endotoxemia in RYGB patients Human Metabolism; Molecular Biology; Cell Biology |
| Databáze: | OpenAIRE |
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