Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection

By Christoph A. Thaiss, M. Levy, I. Grosheva, D. Zheng, Eliran Soffer, E. Blacher, S. Braverman, A. Tengeler, O. Barak, M. Elazar and 13 more. Science, 2018

820 citations recorded by the source corpus.

Metabolic syndrome, leaky guts, and infection Metabolic syndrome often accompanies obesity and hyperglycemia and is associated with a breakdown in the integrity of the intestinal barrier and increased risk of systemic infection. Thaiss et al. found that mice with systemic infection of a Salmonella analog, Citrobacter rodentium, also exhibited hyperglycemia. Deletion of the glucose transporter GLUT2 altered sensitivity to chemically induced epithelial permeability and protected mice from pathogen invasion. The authors also found a correlation in humans between glycated hemoglobin (an indicator of hyperglycemia) and serum levels of pathogen recognition receptor ligands. Science, this issue p. 1376 High blood sugar levels cause epithelial reprogramming, compromising gut barrier integrity and increasing susceptibility to pathogens. Obesity, diabetes, and related manifestations are associated with an enhanced, but poorly understood, risk for mucosal infection and systemic inflammation. Here, we show in mouse models of obesity and diabetes that hyperglycemia drives intestinal barrier permeability, through GLUT2-dependent transcriptional reprogramming of intestinal epithelial cells and alteration of tight and adherence junction integrity. Consequently, hyperglycemia-mediated barrier disruption leads to systemic influx of microbial products and enhanced dissemination of enteric infection. Treatment of hyperglycemia, intestinal epithelial–specific GLUT2 deletion, or inhibition of glucose metabolism restores barrier function and bacterial containment. In humans, systemic influx of intestinal microbiome products correlates with individualized glycemic control, indicated by glycated hemoglobin levels. Together, our results mechanistically link hyperglycemia and intestinal barrier function with systemic infectious and inflammatory consequences of obesity and diabetes.

Subfields: Genetics, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/3694fa1e9f3482326726406602366d3c407001e8

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

1. P. J. Yannie
2. M. Barone
3. Shobha Ghosh
4. S. Ghosh
5. C. Dargenio
6. Jing Wang
7. F. Cristofori
8. V. Miniello

Citations in the corpus

• Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body (2021, background): “TMAO is able to activate macrophage and platelet inflammatory response causing endothelial dysfunction, vascular inflammation, and ultimately increasing the risk of cardiovascular disease (50).”
• Intestinal Barrier Dysfunction, LPS Translocation, and Disease Development (2020, background): “Hyperglycemia increases intestinal permeability via GLUT2-dependent transcriptional reprogramming of the intestinal cells, leading to the reduced expression of tight junction proteins, and in humans the systemic influx of intestinal bacteria-derived products correlates with individualized glycemic c”