<i>Bifidobacterium bifidum</i> 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
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, <i>Bifidobacterium</i>, is one of th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/15/8070 |
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| author | Rana Al-Sadi Viszwapriya Dharmaprakash Prashant Nighot Shuhong Guo Meghali Nighot Toan Do Thomas Y. Ma |
| author_facet | Rana Al-Sadi Viszwapriya Dharmaprakash Prashant Nighot Shuhong Guo Meghali Nighot Toan Do Thomas Y. Ma |
| author_sort | Rana Al-Sadi |
| collection | DOAJ |
| description | 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, <i>Bifidobacterium</i>, 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 <i>Bifidobacterium</i> 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 <i>Bifidobacterium bifidum</i> caused a marked, sustained enhancement in the intestinal TJ barrier in Caco-2 monolayers. The <i>Bifidobacterium bifidum</i> 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. |
| first_indexed | 2024-03-10T09:14:46Z |
| format | Article |
| id | doaj.art-33a7fb3b09174925bf41e44493371cdf |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:14:46Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-33a7fb3b09174925bf41e44493371cdf2023-11-22T05:42:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215807010.3390/ijms22158070<i>Bifidobacterium bifidum</i> 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 MannerRana Al-Sadi0Viszwapriya Dharmaprakash1Prashant Nighot2Shuhong Guo3Meghali Nighot4Toan Do5Thomas Y. Ma6Department of Medicine, Penn State College of Medicine, Hershey Medical Center, Penn State University, Hershey, PA 17033, USADepartment of Medicine, Penn State College of Medicine, Hershey Medical Center, Penn State University, Hershey, PA 17033, USADepartment of Medicine, Penn State College of Medicine, Hershey Medical Center, Penn State University, Hershey, PA 17033, USADepartment of Medicine, Penn State College of Medicine, Hershey Medical Center, Penn State University, Hershey, PA 17033, USADepartment of Medicine, Penn State College of Medicine, Hershey Medical Center, Penn State University, Hershey, PA 17033, USADepartment of Medicine, Penn State College of Medicine, Hershey Medical Center, Penn State University, Hershey, PA 17033, USADepartment of Medicine, Penn State College of Medicine, Hershey Medical Center, Penn State University, Hershey, PA 17033, USADefective 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, <i>Bifidobacterium</i>, 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 <i>Bifidobacterium</i> 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 <i>Bifidobacterium bifidum</i> caused a marked, sustained enhancement in the intestinal TJ barrier in Caco-2 monolayers. The <i>Bifidobacterium bifidum</i> 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.https://www.mdpi.com/1422-0067/22/15/8070<i>Bifidobacterium</i>intestinal barriertoll-like receptor-2 |
| spellingShingle | Rana Al-Sadi Viszwapriya Dharmaprakash Prashant Nighot Shuhong Guo Meghali Nighot Toan Do Thomas Y. Ma <i>Bifidobacterium bifidum</i> 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 International Journal of Molecular Sciences <i>Bifidobacterium</i> intestinal barrier toll-like receptor-2 |
| title | <i>Bifidobacterium bifidum</i> 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 |
| title_full | <i>Bifidobacterium bifidum</i> 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 |
| title_fullStr | <i>Bifidobacterium bifidum</i> 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 |
| title_full_unstemmed | <i>Bifidobacterium bifidum</i> 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 |
| title_short | <i>Bifidobacterium bifidum</i> 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 |
| title_sort | i bifidobacterium bifidum i 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 |
| topic | <i>Bifidobacterium</i> intestinal barrier toll-like receptor-2 |
| url | https://www.mdpi.com/1422-0067/22/15/8070 |
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