Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis
ABSTRACTDysregulation of both the gut barrier and microbiota (dysbiosis) promotes susceptibility to and severity of Inflammatory Bowel Diseases (IBD). Leaky gut and dysbiosis often coexist; however, potential interdependence and molecular regulation are not well understood. Robust expression of clau...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2023.2282789 |
| _version_ | 1827240507739209728 |
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| author | Rizwan Ahmad Balawant Kumar Ishwor Thapa Geoffrey A. Talmon Jeffrey Salomon Amanda E. Ramer-Tait Dhundy K. Bastola Punita Dhawan Amar B. Singh |
| author_facet | Rizwan Ahmad Balawant Kumar Ishwor Thapa Geoffrey A. Talmon Jeffrey Salomon Amanda E. Ramer-Tait Dhundy K. Bastola Punita Dhawan Amar B. Singh |
| author_sort | Rizwan Ahmad |
| collection | DOAJ |
| description | ABSTRACTDysregulation of both the gut barrier and microbiota (dysbiosis) promotes susceptibility to and severity of Inflammatory Bowel Diseases (IBD). Leaky gut and dysbiosis often coexist; however, potential interdependence and molecular regulation are not well understood. Robust expression of claudin-3 (CLDN3) characterizes the gut epithelium, and studies have demonstrated a positive association between CLDN3 expression and gut barrier maturity and integrity, including in response to probiotics. However, the exact status and causal role of CLDN3 in IBD and regulation of gut dysbiosis remain unknown. Analysis of mouse and human IBD cohorts helped examine CLDN3 expression in IBD. The causal role was determined by modeling CLDN3 loss of expression during experimental colitis. 16S sequencing and in silico analysis helped examine gut microbiota diversity between Cldn3KO and WT mice and potential host metabolic responses. Fecal microbiota transplant (FMT) studies were performed to assess the role of gut dysbiosis in the increased susceptibility of Cldn3KO mice to colitis. A significant decrease in CLDN3 expression characterized IBD and CLDN3 loss of expression promoted colitis. 16S sequencing analysis suggested gut microbiota changes in Cldn3KO mice that were capable of modulating fatty acid metabolism and oxidative stress response. FMT from naïve Cldn3KO mice promoted colitis susceptibility in recipient germ-free mice (GFM) compared with GFM-receiving microbiota from WT mice. Our data demonstrate a critical role of CLDN3 in maintaining normal gut microbiota and inflammatory responses, which can be harnessed to develop novel therapeutic opportunities for patients with IBD. |
| first_indexed | 2024-03-08T04:40:34Z |
| format | Article |
| id | doaj.art-16660186e92e4850a9ee086696636cc2 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2025-03-21T21:25:42Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-16660186e92e4850a9ee086696636cc22024-05-28T15:04:40ZengTaylor & Francis GroupGut Microbes1949-09761949-09842023-12-0115210.1080/19490976.2023.2282789Loss of claudin-3 expression increases colitis risk by promoting Gut DysbiosisRizwan Ahmad0Balawant Kumar1Ishwor Thapa2Geoffrey A. Talmon3Jeffrey Salomon4Amanda E. Ramer-Tait5Dhundy K. Bastola6Punita Dhawan7Amar B. Singh8Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USADepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USASchool of Interdisciplinary Informatics, College of Information Science & Technology, University of Nebraska at Omaha, Omaha, NE, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USADepartment of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USADepartment of Food Science and Technology and the Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, NE, USASchool of Interdisciplinary Informatics, College of Information Science & Technology, University of Nebraska at Omaha, Omaha, NE, USADepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USADepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USAABSTRACTDysregulation of both the gut barrier and microbiota (dysbiosis) promotes susceptibility to and severity of Inflammatory Bowel Diseases (IBD). Leaky gut and dysbiosis often coexist; however, potential interdependence and molecular regulation are not well understood. Robust expression of claudin-3 (CLDN3) characterizes the gut epithelium, and studies have demonstrated a positive association between CLDN3 expression and gut barrier maturity and integrity, including in response to probiotics. However, the exact status and causal role of CLDN3 in IBD and regulation of gut dysbiosis remain unknown. Analysis of mouse and human IBD cohorts helped examine CLDN3 expression in IBD. The causal role was determined by modeling CLDN3 loss of expression during experimental colitis. 16S sequencing and in silico analysis helped examine gut microbiota diversity between Cldn3KO and WT mice and potential host metabolic responses. Fecal microbiota transplant (FMT) studies were performed to assess the role of gut dysbiosis in the increased susceptibility of Cldn3KO mice to colitis. A significant decrease in CLDN3 expression characterized IBD and CLDN3 loss of expression promoted colitis. 16S sequencing analysis suggested gut microbiota changes in Cldn3KO mice that were capable of modulating fatty acid metabolism and oxidative stress response. FMT from naïve Cldn3KO mice promoted colitis susceptibility in recipient germ-free mice (GFM) compared with GFM-receiving microbiota from WT mice. Our data demonstrate a critical role of CLDN3 in maintaining normal gut microbiota and inflammatory responses, which can be harnessed to develop novel therapeutic opportunities for patients with IBD.https://www.tandfonline.com/doi/10.1080/19490976.2023.2282789Claudingut barrierdysbiosisFMTgerm-free mice and IBD |
| spellingShingle | Rizwan Ahmad Balawant Kumar Ishwor Thapa Geoffrey A. Talmon Jeffrey Salomon Amanda E. Ramer-Tait Dhundy K. Bastola Punita Dhawan Amar B. Singh Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis Gut Microbes Claudin gut barrier dysbiosis FMT germ-free mice and IBD |
| title | Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis |
| title_full | Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis |
| title_fullStr | Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis |
| title_full_unstemmed | Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis |
| title_short | Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis |
| title_sort | loss of claudin 3 expression increases colitis risk by promoting gut dysbiosis |
| topic | Claudin gut barrier dysbiosis FMT germ-free mice and IBD |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2023.2282789 |
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