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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

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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.

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Acknowledgements

We are grateful to our colleagues at Pasteur Institute of Iran.

Funding

This work was supported by the National Institute for Medical Research Development (NIMAD) (grant number: 942995).

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Authors and Affiliations

  1. Department of Cell & Molecular Sciences Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

    Amin Malek, Gilda Karimi & Saeed Irian

  2. Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran

    Amin Malek & Sara Ahmadi Badi

  3. Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Sara Ahmadi Badi

  4. Universit´e Paris-Saclay, CNRS, Institut de Chimie Physique, UMR8000, Orsay, 91405, France

    Tania Bizouarn

  5. Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran

    Seyed Davar Siadat

  6. Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, Tehran, Iran

    Seyed Davar Siadat

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  1. Amin Malek
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Correspondence to Sara Ahmadi Badi.

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Malek, A., Ahmadi Badi, S., Karimi, G. et al. 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. J Diabetes Metab Disord 22, 1417–1424 (2023). https://doi.org/10.1007/s40200-023-01264-8

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