Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction
Hyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals with or without T2D were included from two independent Dutch cohorts. Human data were translated in vit...
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| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2111951 |
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| author | Torsten P.M. Scheithauer Hilde Herrema Hongbing Yu Guido J. Bakker Maaike Winkelmeijer Galina Soukhatcheva Derek Dai Caixia Ma Stefan R. Havik Manon Balvers Mark Davids Abraham S. Meijnikman Ömrüm Aydin Bert-Jan H. van den Born Marc G. Besselink Olivier R. Busch Maurits de Brauw Arnold van de Laar Clara Belzer Martin Stahl Willem M. de Vos Bruce A. Vallance Max Nieuwdorp C. Bruce Verchere Daniël H. van Raalte |
| author_facet | Torsten P.M. Scheithauer Hilde Herrema Hongbing Yu Guido J. Bakker Maaike Winkelmeijer Galina Soukhatcheva Derek Dai Caixia Ma Stefan R. Havik Manon Balvers Mark Davids Abraham S. Meijnikman Ömrüm Aydin Bert-Jan H. van den Born Marc G. Besselink Olivier R. Busch Maurits de Brauw Arnold van de Laar Clara Belzer Martin Stahl Willem M. de Vos Bruce A. Vallance Max Nieuwdorp C. Bruce Verchere Daniël H. van Raalte |
| author_sort | Torsten P.M. Scheithauer |
| collection | DOAJ |
| description | Hyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals with or without T2D were included from two independent Dutch cohorts. Human data were translated in vitro and in vivo by using pancreatic islets from C57BL6/J mice and by injecting flagellin into obese mice. Flagellin is part of the bacterial locomotor appendage flagellum, present in gut bacteria including Enterobacteriaceae, which we show to be more abundant in the gut of individuals with T2D. Subsequently, flagellin induces a pro-inflammatory response in pancreatic islets mediated by the Toll-like receptor (TLR)-5 expressed on resident islet macrophages. This inflammatory response is associated with beta-cell dysfunction, characterized by reduced insulin gene expression, impaired proinsulin processing and stress-induced insulin hypersecretion in vitro and in vivo in mice. We postulate that increased systemically disseminated flagellin in T2D is a contributing factor to beta-cell failure in time and represents a novel therapeutic target. |
| format | Article |
| id | doaj-art-51e301893b1e4bf7bc15c80a62ac3ab1 |
| institution | DOAJ |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-51e301893b1e4bf7bc15c80a62ac3ab12025-08-20T03:12:50ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2111951Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunctionTorsten P.M. Scheithauer0Hilde Herrema1Hongbing Yu2Guido J. Bakker3Maaike Winkelmeijer4Galina Soukhatcheva5Derek Dai6Caixia Ma7Stefan R. Havik8Manon Balvers9Mark Davids10Abraham S. Meijnikman11Ömrüm Aydin12Bert-Jan H. van den Born13Marc G. Besselink14Olivier R. Busch15Maurits de Brauw16Arnold van de Laar17Clara Belzer18Martin Stahl19Willem M. de Vos20Bruce A. Vallance21Max Nieuwdorp22C. Bruce Verchere23Daniël H. van Raalte24Department of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, and BC Children’s Hospital Research Institute, Vancouver, British Columbia, CanadaDepartment of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartments of Surgery and Pathology and Laboratory Medicine Pathology and Laboratory Medicine, BC Children’s Hospital Research Institute, Centre for Molecular Medicine & Therapeutics, Vancouver, British Columbia, CanadaDepartments of Surgery and Pathology and Laboratory Medicine Pathology and Laboratory Medicine, BC Children’s Hospital Research Institute, Centre for Molecular Medicine & Therapeutics, Vancouver, British Columbia, CanadaDepartment of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, and BC Children’s Hospital Research Institute, Vancouver, British Columbia, CanadaDepartment of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, the NetherlandsDepartment of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, the NetherlandsDepartment of Surgery, Spaarne Gasthuis, Hoofddorp, The NetherlandsDepartment of Surgery, Spaarne Gasthuis, Hoofddorp, The NetherlandsLaboratory of Microbiology, Wageningen University and Research, Wageningen, The NetherlandsDepartment of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, and BC Children’s Hospital Research Institute, Vancouver, British Columbia, CanadaLaboratory of Microbiology, Wageningen University and Research, Wageningen, The NetherlandsDepartment of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, and BC Children’s Hospital Research Institute, Vancouver, British Columbia, CanadaDepartment of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartments of Surgery and Pathology and Laboratory Medicine Pathology and Laboratory Medicine, BC Children’s Hospital Research Institute, Centre for Molecular Medicine & Therapeutics, Vancouver, British Columbia, CanadaDepartment of (Experimental) Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsHyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals with or without T2D were included from two independent Dutch cohorts. Human data were translated in vitro and in vivo by using pancreatic islets from C57BL6/J mice and by injecting flagellin into obese mice. Flagellin is part of the bacterial locomotor appendage flagellum, present in gut bacteria including Enterobacteriaceae, which we show to be more abundant in the gut of individuals with T2D. Subsequently, flagellin induces a pro-inflammatory response in pancreatic islets mediated by the Toll-like receptor (TLR)-5 expressed on resident islet macrophages. This inflammatory response is associated with beta-cell dysfunction, characterized by reduced insulin gene expression, impaired proinsulin processing and stress-induced insulin hypersecretion in vitro and in vivo in mice. We postulate that increased systemically disseminated flagellin in T2D is a contributing factor to beta-cell failure in time and represents a novel therapeutic target.https://www.tandfonline.com/doi/10.1080/19490976.2022.2111951Gut microbiotatype 2 diabetesinflammationbeta-cell functionflagellin |
| spellingShingle | Torsten P.M. Scheithauer Hilde Herrema Hongbing Yu Guido J. Bakker Maaike Winkelmeijer Galina Soukhatcheva Derek Dai Caixia Ma Stefan R. Havik Manon Balvers Mark Davids Abraham S. Meijnikman Ömrüm Aydin Bert-Jan H. van den Born Marc G. Besselink Olivier R. Busch Maurits de Brauw Arnold van de Laar Clara Belzer Martin Stahl Willem M. de Vos Bruce A. Vallance Max Nieuwdorp C. Bruce Verchere Daniël H. van Raalte Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction Gut Microbes Gut microbiota type 2 diabetes inflammation beta-cell function flagellin |
| title | Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction |
| title_full | Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction |
| title_fullStr | Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction |
| title_full_unstemmed | Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction |
| title_short | Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction |
| title_sort | gut derived bacterial flagellin induces beta cell inflammation and dysfunction |
| topic | Gut microbiota type 2 diabetes inflammation beta-cell function flagellin |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2111951 |
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