Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet
This study aimed to determine the association between non-high-fat diet-induced obesity- (non-DIO-) associated gut microbiome dysbiosis with gut abnormalities like cellular turnover of intestinal cells, tight junctions, and mucin formation that can impact gut permeability. We used leptin-deficient (...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2018/3462092 |
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| _version_ | 1832550274382692352 |
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| author | Ravinder Nagpal Tiffany M. Newman Shaohua Wang Shalini Jain James F. Lovato Hariom Yadav |
| author_facet | Ravinder Nagpal Tiffany M. Newman Shaohua Wang Shalini Jain James F. Lovato Hariom Yadav |
| author_sort | Ravinder Nagpal |
| collection | DOAJ |
| description | This study aimed to determine the association between non-high-fat diet-induced obesity- (non-DIO-) associated gut microbiome dysbiosis with gut abnormalities like cellular turnover of intestinal cells, tight junctions, and mucin formation that can impact gut permeability. We used leptin-deficient (Lepob/ob) mice in comparison to C57BL/6J control mice, which are fed on identical diets, and performed comparative and correlative analyses of gut microbiome composition, gut permeability, intestinal structural changes, tight junction-mucin formation, cellular turnover, and stemness genes. We found that obesity impacted cellular turnover of the intestine with increased cell death and cell survival/proliferation gene expression with enhanced stemness, which are associated with increased intestinal permeability, changes in villi/crypt length, and decreased expression of tight junctions and mucus synthesis genes along with dysbiotic gut microbiome signature. Obesity-induced gut microbiome dysbiosis is also associated with abnormal intestinal organoid formation characterized with decreased budding and higher stemness. Results suggest that non-DIO-associated gut microbiome dysbiosis is associated with changes in the intestinal cell death versus cell proliferation homeostasis and functions to control tight junctions and mucous synthesis-regulating gut permeability. |
| format | Article |
| id | doaj-art-54f85e1a2c7840d3bc9ec0b05f2a0aed |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-54f85e1a2c7840d3bc9ec0b05f2a0aed2025-02-03T06:07:10ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/34620923462092Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of DietRavinder Nagpal0Tiffany M. Newman1Shaohua Wang2Shalini Jain3James F. Lovato4Hariom Yadav5Department of Internal Medicine-Molecular Medicine and Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC, USADepartment of Internal Medicine-Molecular Medicine and Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC, USADepartment of Internal Medicine-Molecular Medicine and Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC, USADepartment of Internal Medicine-Molecular Medicine and Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC, USADivision of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USADepartment of Internal Medicine-Molecular Medicine and Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC, USAThis study aimed to determine the association between non-high-fat diet-induced obesity- (non-DIO-) associated gut microbiome dysbiosis with gut abnormalities like cellular turnover of intestinal cells, tight junctions, and mucin formation that can impact gut permeability. We used leptin-deficient (Lepob/ob) mice in comparison to C57BL/6J control mice, which are fed on identical diets, and performed comparative and correlative analyses of gut microbiome composition, gut permeability, intestinal structural changes, tight junction-mucin formation, cellular turnover, and stemness genes. We found that obesity impacted cellular turnover of the intestine with increased cell death and cell survival/proliferation gene expression with enhanced stemness, which are associated with increased intestinal permeability, changes in villi/crypt length, and decreased expression of tight junctions and mucus synthesis genes along with dysbiotic gut microbiome signature. Obesity-induced gut microbiome dysbiosis is also associated with abnormal intestinal organoid formation characterized with decreased budding and higher stemness. Results suggest that non-DIO-associated gut microbiome dysbiosis is associated with changes in the intestinal cell death versus cell proliferation homeostasis and functions to control tight junctions and mucous synthesis-regulating gut permeability.http://dx.doi.org/10.1155/2018/3462092 |
| spellingShingle | Ravinder Nagpal Tiffany M. Newman Shaohua Wang Shalini Jain James F. Lovato Hariom Yadav Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet Journal of Diabetes Research |
| title | Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet |
| title_full | Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet |
| title_fullStr | Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet |
| title_full_unstemmed | Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet |
| title_short | Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet |
| title_sort | obesity linked gut microbiome dysbiosis associated with derangements in gut permeability and intestinal cellular homeostasis independent of diet |
| url | http://dx.doi.org/10.1155/2018/3462092 |
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