Changes in Intestinal Microbiota Are Associated with Islet Function in a Mouse Model of Dietary Vitamin A Deficiency
Aims. The underlying mechanisms involved in Vitamin A- (VA-) related changes in glucose metabolic disorders remain unclear. Recent evidence suggests that intestinal microbiota is closely linked to the metabolic syndrome. Here, we explored whether and how intestinal microbiota affects glucose homeost...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2020/2354108 |
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| author | Yunting Zhou Junming Zhou Yumin Zhang Jun Tang Bo Sun Wei Xu Xiaohang Wang Yang Chen Zilin Sun |
| author_facet | Yunting Zhou Junming Zhou Yumin Zhang Jun Tang Bo Sun Wei Xu Xiaohang Wang Yang Chen Zilin Sun |
| author_sort | Yunting Zhou |
| collection | DOAJ |
| description | Aims. The underlying mechanisms involved in Vitamin A- (VA-) related changes in glucose metabolic disorders remain unclear. Recent evidence suggests that intestinal microbiota is closely linked to the metabolic syndrome. Here, we explored whether and how intestinal microbiota affects glucose homeostasis in VA-deficient diet-fed mice. Methods. Six-week-old male C57BL/6 mice were randomly placed on either a VA-sufficient (VAS) or VA-deficient (VAD) diet for 10 weeks. Subsequently, a subclass of the VAD diet-fed mice was switched to a VA-deficient rescued (VADR) diet for an additional 8 weeks. The glucose metabolic phenotypes of the mice were assessed using glucose tolerance tests and immunohistochemistry staining. Changes in intestinal microbiota were assessed using 16S gene sequencing. The intestinal morphology, intestinal permeability, and inflammatory response activation signaling pathway were assessed using histological staining, western blots, quantitative-PCR, and enzyme-linked immunosorbent assays. Results. VAD diet-fed mice displayed reduction of tissue VA levels, increased area under the curve (AUC) of glucose challenge, reduced glucose-stimulated insulin secretion, and loss of β cell mass. Redundancy analysis showed intestinal microbiota diversity was significantly associated with AUC of glucose challenge and β cell mass. VAD diet-driven changes in intestinal microbiota followed the inflammatory response with increased intestinal permeability and higher mRNA expression of intestinal inflammatory cytokines through nuclear factor-κB signaling pathway activation. Reintroduction of dietary VA to VAD diet-fed mice restored tissue VA levels, endocrine hormone profiles, and inflammatory response, which are similar to those observed following VAS-controlled changes in intestinal microbiota. Conclusions. We found intestinal microbiota effect islet function via controlling intestinal inflammatory phenotype in VAD diet-fed mice. Intestinal microbiota influences could be considered as an additional mechanism for the effect of endocrine function in a VAD diet-driven mouse model. |
| format | Article |
| id | doaj-art-e40a66b9828049c499f6e3522ecb1414 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-e40a66b9828049c499f6e3522ecb14142025-02-03T01:04:05ZengWileyJournal of Diabetes Research2314-67452314-67532020-01-01202010.1155/2020/23541082354108Changes in Intestinal Microbiota Are Associated with Islet Function in a Mouse Model of Dietary Vitamin A DeficiencyYunting Zhou0Junming Zhou1Yumin Zhang2Jun Tang3Bo Sun4Wei Xu5Xiaohang Wang6Yang Chen7Zilin Sun8Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, ChinaDepartment of Gastroenterology, Jinling Hospital, Medical School of Nanjing University, Nanjing, ChinaDepartment of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, ChinaDepartment of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaDepartment of Diabetes, School of Life Course Sciences, King’s College London, Guy’s Campus, London, UKDepartment of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, ChinaDepartment of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, ChinaDepartment of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, ChinaAims. The underlying mechanisms involved in Vitamin A- (VA-) related changes in glucose metabolic disorders remain unclear. Recent evidence suggests that intestinal microbiota is closely linked to the metabolic syndrome. Here, we explored whether and how intestinal microbiota affects glucose homeostasis in VA-deficient diet-fed mice. Methods. Six-week-old male C57BL/6 mice were randomly placed on either a VA-sufficient (VAS) or VA-deficient (VAD) diet for 10 weeks. Subsequently, a subclass of the VAD diet-fed mice was switched to a VA-deficient rescued (VADR) diet for an additional 8 weeks. The glucose metabolic phenotypes of the mice were assessed using glucose tolerance tests and immunohistochemistry staining. Changes in intestinal microbiota were assessed using 16S gene sequencing. The intestinal morphology, intestinal permeability, and inflammatory response activation signaling pathway were assessed using histological staining, western blots, quantitative-PCR, and enzyme-linked immunosorbent assays. Results. VAD diet-fed mice displayed reduction of tissue VA levels, increased area under the curve (AUC) of glucose challenge, reduced glucose-stimulated insulin secretion, and loss of β cell mass. Redundancy analysis showed intestinal microbiota diversity was significantly associated with AUC of glucose challenge and β cell mass. VAD diet-driven changes in intestinal microbiota followed the inflammatory response with increased intestinal permeability and higher mRNA expression of intestinal inflammatory cytokines through nuclear factor-κB signaling pathway activation. Reintroduction of dietary VA to VAD diet-fed mice restored tissue VA levels, endocrine hormone profiles, and inflammatory response, which are similar to those observed following VAS-controlled changes in intestinal microbiota. Conclusions. We found intestinal microbiota effect islet function via controlling intestinal inflammatory phenotype in VAD diet-fed mice. Intestinal microbiota influences could be considered as an additional mechanism for the effect of endocrine function in a VAD diet-driven mouse model.http://dx.doi.org/10.1155/2020/2354108 |
| spellingShingle | Yunting Zhou Junming Zhou Yumin Zhang Jun Tang Bo Sun Wei Xu Xiaohang Wang Yang Chen Zilin Sun Changes in Intestinal Microbiota Are Associated with Islet Function in a Mouse Model of Dietary Vitamin A Deficiency Journal of Diabetes Research |
| title | Changes in Intestinal Microbiota Are Associated with Islet Function in a Mouse Model of Dietary Vitamin A Deficiency |
| title_full | Changes in Intestinal Microbiota Are Associated with Islet Function in a Mouse Model of Dietary Vitamin A Deficiency |
| title_fullStr | Changes in Intestinal Microbiota Are Associated with Islet Function in a Mouse Model of Dietary Vitamin A Deficiency |
| title_full_unstemmed | Changes in Intestinal Microbiota Are Associated with Islet Function in a Mouse Model of Dietary Vitamin A Deficiency |
| title_short | Changes in Intestinal Microbiota Are Associated with Islet Function in a Mouse Model of Dietary Vitamin A Deficiency |
| title_sort | changes in intestinal microbiota are associated with islet function in a mouse model of dietary vitamin a deficiency |
| url | http://dx.doi.org/10.1155/2020/2354108 |
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