Decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model

Abstract Psychological stress has been reported to relate to dysbiosis, imbalance of the intestinal microbiota composition, and contribute to the onset and exacerbation of depression, though, underlying mechanisms of psychological stress-related dysbiosis have been unknown. It has been previously es...

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Autores principales:	Kosuke Suzuki, Kiminori Nakamura, Yu Shimizu, Yuki Yokoi, Shuya Ohira, Mizu Hagiwara, Yi Wang, Yuchi Song, Tomoyasu Aizawa, Tokiyoshi Ayabe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7a71c12027b64439b42c83c6fb53d9e9
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spelling	oai:doaj.org-article:7a71c12027b64439b42c83c6fb53d9e92021-12-02T14:35:47ZDecrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model10.1038/s41598-021-89308-y2045-2322https://doaj.org/article/7a71c12027b64439b42c83c6fb53d9e92021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89308-yhttps://doaj.org/toc/2045-2322Abstract Psychological stress has been reported to relate to dysbiosis, imbalance of the intestinal microbiota composition, and contribute to the onset and exacerbation of depression, though, underlying mechanisms of psychological stress-related dysbiosis have been unknown. It has been previously established that α-defensins, which are effector peptides of innate enteric immunity produced by Paneth cells in the small intestine, play an important role in regulation of the intestinal microbiota. However, the relationship between disruption of intestinal ecosystem and α-defensin under psychological stress is yet to be determined. Here we show using chronic social defeat stress (CSDS), a mouse depression model that (1) the exposure to CSDS significantly reduces α-defensin secretion by Paneth cells and (2) induces dysbiosis and significant composition changes in the intestinal metabolites. Furthermore, (3) they are recovered by administration of α-defensin. These results indicate that α-defensin plays an important role in maintaining homeostasis of the intestinal ecosystem under psychological stress, providing novel insights into the onset mechanism of stress-induced depression, and may further contribute to discovery of treatment targets for depression.Kosuke SuzukiKiminori NakamuraYu ShimizuYuki YokoiShuya OhiraMizu HagiwaraYi WangYuchi SongTomoyasu AizawaTokiyoshi AyabeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kosuke Suzuki Kiminori Nakamura Yu Shimizu Yuki Yokoi Shuya Ohira Mizu Hagiwara Yi Wang Yuchi Song Tomoyasu Aizawa Tokiyoshi Ayabe Decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model
description	Abstract Psychological stress has been reported to relate to dysbiosis, imbalance of the intestinal microbiota composition, and contribute to the onset and exacerbation of depression, though, underlying mechanisms of psychological stress-related dysbiosis have been unknown. It has been previously established that α-defensins, which are effector peptides of innate enteric immunity produced by Paneth cells in the small intestine, play an important role in regulation of the intestinal microbiota. However, the relationship between disruption of intestinal ecosystem and α-defensin under psychological stress is yet to be determined. Here we show using chronic social defeat stress (CSDS), a mouse depression model that (1) the exposure to CSDS significantly reduces α-defensin secretion by Paneth cells and (2) induces dysbiosis and significant composition changes in the intestinal metabolites. Furthermore, (3) they are recovered by administration of α-defensin. These results indicate that α-defensin plays an important role in maintaining homeostasis of the intestinal ecosystem under psychological stress, providing novel insights into the onset mechanism of stress-induced depression, and may further contribute to discovery of treatment targets for depression.
format	article
author	Kosuke Suzuki Kiminori Nakamura Yu Shimizu Yuki Yokoi Shuya Ohira Mizu Hagiwara Yi Wang Yuchi Song Tomoyasu Aizawa Tokiyoshi Ayabe
author_facet	Kosuke Suzuki Kiminori Nakamura Yu Shimizu Yuki Yokoi Shuya Ohira Mizu Hagiwara Yi Wang Yuchi Song Tomoyasu Aizawa Tokiyoshi Ayabe
author_sort	Kosuke Suzuki
title	Decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model
title_short	Decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model
title_full	Decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model
title_fullStr	Decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model
title_full_unstemmed	Decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model
title_sort	decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7a71c12027b64439b42c83c6fb53d9e9
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Decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model

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