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The Effect of Bacteroides Fragilis and Its Postbiotics on the Expression of Genes Involved in the Endocannabinoid System and Intestinal Epithelial Integrity in Caco-2 Cells Publisher



Malek A1, 2 ; Ahmadi Badi S2, 3 ; Karimi G1 ; Bizouarn T4 ; Irian S1 ; Siadat SD5, 6
Authors
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Authors Affiliations
  1. 1. Department of Cell & Molecular Sciences Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
  2. 2. Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran
  3. 3. Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Universit´e Paris-Saclay, CNRS, Institut de Chimie Physique, UMR8000, Orsay, 91405, France
  5. 5. Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran
  6. 6. Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, Tehran, Iran

Source: Journal of Diabetes and Metabolic Disorders Published:2023


Abstract

Purpose: Gut microbiota and its derivatives by constantly interacting with the host, regulate the host function. Intestinal epithelium integrity is under the control of various factors including the endocannabinoid system (ECS). Accordingly, we aimed at investigating the effect of Bacteroides fragilis and its postbiotics (i.e., heat-inactivated, cell-free supernatants (CFS) and outer membrane vesicles (OMVs)) on the expression of genes involved in ECS (cnr1, faah, pparg) and the epithelial barrier permeability (ocln, tjp1) in a Caco-2 cell line. Methods: Caco-2 cell line was treated with live or heat-inactivated B. fragilis at MOIs of 50 and 100, or stimulated with 7% V/V CFS and B. fragilis OMVs at a dose of 50 and 100 µg/ml overnight. RT-qPCR was applied for expression analysis. Results: Heat-inactivated B. fragilis induced cnr1, pparg, tjp1, and suppressed faah expression, while live B. fragilis had the opposite effect. OMVs increased pparg, and tjp1 expression by reducing the activity of ECS through an increase in faah and a reduction in cnr1 expression. Finally, an increase in the expression of pparg and ocln, and a reduction in the expression of cnr1 was detected in Caco-2 cells treated with CFS. Conclusion: The live and heat-inactivated B. fragilis inversely affected cnr1, faah, pparg, and tjp1 expression in Caco-2 cells. Increased tjp1 mRNA levels by affecting the expression of ECS related genes is taken as an indication of the potential beneficial effects of B. fragilis postbiotics and making them potential candidates for improving permeability in the leaky gut syndrome. © 2023, The Author(s), under exclusive licence to Tehran University of Medical Sciences.