Bifidobacterium bifidum Enhances the Intestinal Epithelial Tight Junction Barrier and Protects against Intestinal Inflammation by Targeting the Toll-like Receptor-2 Pathway in an NF-κB-Independent Manner
| Autor: | Rana Al-Sadi, Prashant Nighot, Thomas Y. Ma, Meghali Nighot, Viszwapriya Dharmaprakash, Toan Do, Shuhong Guo |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Receptor complex Enterocyte QH301-705.5 ved/biology.organism_classification_rank.species Catalysis Article Inorganic Chemistry 03 medical and health sciences 0302 clinical medicine medicine Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy Barrier function Bifidobacterium Toll-like receptor Bifidobacterium bifidum biology Tight junction Chemistry ved/biology Organic Chemistry General Medicine Apical membrane biology.organism_classification Computer Science Applications Cell biology intestinal barrier 030104 developmental biology medicine.anatomical_structure toll-like receptor-2 030211 gastroenterology & hepatology |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 8070, p 8070 (2021) International Journal of Molecular Sciences Volume 22 Issue 15 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Defective intestinal tight junction (TJ) barrier is a hallmark in the pathogenesis of inflammatory bowel disease (IBD). To date, there are no effective therapies that specifically target the intestinal TJ barrier. Among the various probiotic bacteria, Bifidobacterium, is one of the most widely studied to have beneficial effects on the intestinal TJ barrier. The main purpose of this study was to identify Bifidobacterium species that cause a sustained enhancement in the intestinal epithelial TJ barrier and can be used therapeutically to target the intestinal TJ barrier and to protect against or treat intestinal inflammation. Our results showed that Bifidobacterium bifidum caused a marked, sustained enhancement in the intestinal TJ barrier in Caco-2 monolayers. The Bifidobacterium bifidum effect on TJ barrier was strain-specific, and only the strain designated as BB1 caused a maximal enhancement in TJ barrier function. The mechanism of BB1 enhancement of intestinal TJ barrier required live bacterial cell/enterocyte interaction and was mediated by the BB1 attachment to Toll-like receptor-2 (TLR-2) at the apical membrane surface. The BB1 enhancement of the intestinal epithelial TJ barrier function was mediated by the activation of the p38 kinase pathway, but not the NF-κB signaling pathway. Moreover, the BB1 caused a marked enhancement in mouse intestinal TJ barrier in a TLR-2-dependent manner and protected against dextran sodium sulfate (DSS)-induced increase in mouse colonic permeability, and treated the DSS-induced colitis in a TJ barrier-dependent manner. These studies show that probiotic bacteria BB1 causes a strain-specific enhancement of the intestinal TJ barrier through a novel mechanism involving BB1 attachment to the enterocyte TLR-2 receptor complex and activation of p38 kinase pathway. |
| Databáze: | OpenAIRE |
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