Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat

Abstract Background Chronic unpredictable mild stress (CUMS) can not only lead to depression-like behavior but also change the composition of the gut microbiome. Regulating the gut microbiome can have an antidepressant effect, but the mechanism by which it improves depressive symptoms is not clear....

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Autores principales:	Haonan Li, Yujiao Xiang, Zemeng Zhu, Wei Wang, Zhijun Jiang, Mingyue Zhao, Shuyue Cheng, Fang Pan, Dexiang Liu, Roger C. M. Ho, Cyrus S. H. Ho
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Adolescence Chronic unpredictable mild stress (CUMS) Rifaximin Gut microbiome Short chain fatty acid (SCFA) Microglia Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/0489f7a364a84c49a2374c71294d9e43
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spelling	oai:doaj.org-article:0489f7a364a84c49a2374c71294d9e432021-11-08T11:14:21ZRifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat10.1186/s12974-021-02303-y1742-2094https://doaj.org/article/0489f7a364a84c49a2374c71294d9e432021-11-01T00:00:00Zhttps://doi.org/10.1186/s12974-021-02303-yhttps://doaj.org/toc/1742-2094Abstract Background Chronic unpredictable mild stress (CUMS) can not only lead to depression-like behavior but also change the composition of the gut microbiome. Regulating the gut microbiome can have an antidepressant effect, but the mechanism by which it improves depressive symptoms is not clear. Short-chain fatty acids (SCFAs) are small molecular compounds produced by the fermentation of non-digestible carbohydrates. SFCAs are ubiquitous in intestinal endocrine and immune cells, making them important mediators of gut microbiome-regulated body functions. The balance between the pro- and anti-inflammatory microglia plays an important role in the occurrence and treatment of depression caused by chronic stress. Non-absorbable antibiotic rifaximin can regulate the structure of the gut microbiome. We hypothesized that rifaximin protects against stress-induced inflammation and depression-like behaviors by regulating the abundance of fecal microbial metabolites and the microglial functions. Methods We administered 150 mg/kg rifaximin intragastrically to rats exposed to CUMS for 4 weeks and investigated the composition of the fecal microbiome, the content of short-chain fatty acids in the serum and brain, the functional profiles of microglia and hippocampal neurogenesis. Results Our results show that rifaximin ameliorated depressive-like behavior induced by CUMS, as reflected by sucrose preference, the open field test and the Morris water maze. Rifaximin increased the relative abundance of Ruminococcaceae and Lachnospiraceae, which were significantly positively correlated with the high level of butyrate in the brain. Rifaximin increased the content of anti-inflammatory factors released by microglia, and prevented the neurogenic abnormalities caused by CUMS. Conclusions These results suggest that rifaximin can regulate the inflammatory function of microglia and play a protective role in pubertal neurodevelopment during CUMS by regulating the gut microbiome and short-chain fatty acids.Haonan LiYujiao XiangZemeng ZhuWei WangZhijun JiangMingyue ZhaoShuyue ChengFang PanDexiang LiuRoger C. M. HoCyrus S. H. HoBMCarticleAdolescenceChronic unpredictable mild stress (CUMS)RifaximinGut microbiomeShort chain fatty acid (SCFA)MicrogliaNeurology. Diseases of the nervous systemRC346-429ENJournal of Neuroinflammation, Vol 18, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Adolescence Chronic unpredictable mild stress (CUMS) Rifaximin Gut microbiome Short chain fatty acid (SCFA) Microglia Neurology. Diseases of the nervous system RC346-429
spellingShingle	Adolescence Chronic unpredictable mild stress (CUMS) Rifaximin Gut microbiome Short chain fatty acid (SCFA) Microglia Neurology. Diseases of the nervous system RC346-429 Haonan Li Yujiao Xiang Zemeng Zhu Wei Wang Zhijun Jiang Mingyue Zhao Shuyue Cheng Fang Pan Dexiang Liu Roger C. M. Ho Cyrus S. H. Ho Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat
description	Abstract Background Chronic unpredictable mild stress (CUMS) can not only lead to depression-like behavior but also change the composition of the gut microbiome. Regulating the gut microbiome can have an antidepressant effect, but the mechanism by which it improves depressive symptoms is not clear. Short-chain fatty acids (SCFAs) are small molecular compounds produced by the fermentation of non-digestible carbohydrates. SFCAs are ubiquitous in intestinal endocrine and immune cells, making them important mediators of gut microbiome-regulated body functions. The balance between the pro- and anti-inflammatory microglia plays an important role in the occurrence and treatment of depression caused by chronic stress. Non-absorbable antibiotic rifaximin can regulate the structure of the gut microbiome. We hypothesized that rifaximin protects against stress-induced inflammation and depression-like behaviors by regulating the abundance of fecal microbial metabolites and the microglial functions. Methods We administered 150 mg/kg rifaximin intragastrically to rats exposed to CUMS for 4 weeks and investigated the composition of the fecal microbiome, the content of short-chain fatty acids in the serum and brain, the functional profiles of microglia and hippocampal neurogenesis. Results Our results show that rifaximin ameliorated depressive-like behavior induced by CUMS, as reflected by sucrose preference, the open field test and the Morris water maze. Rifaximin increased the relative abundance of Ruminococcaceae and Lachnospiraceae, which were significantly positively correlated with the high level of butyrate in the brain. Rifaximin increased the content of anti-inflammatory factors released by microglia, and prevented the neurogenic abnormalities caused by CUMS. Conclusions These results suggest that rifaximin can regulate the inflammatory function of microglia and play a protective role in pubertal neurodevelopment during CUMS by regulating the gut microbiome and short-chain fatty acids.
format	article
author	Haonan Li Yujiao Xiang Zemeng Zhu Wei Wang Zhijun Jiang Mingyue Zhao Shuyue Cheng Fang Pan Dexiang Liu Roger C. M. Ho Cyrus S. H. Ho
author_facet	Haonan Li Yujiao Xiang Zemeng Zhu Wei Wang Zhijun Jiang Mingyue Zhao Shuyue Cheng Fang Pan Dexiang Liu Roger C. M. Ho Cyrus S. H. Ho
author_sort	Haonan Li
title	Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat
title_short	Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat
title_full	Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat
title_fullStr	Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat
title_full_unstemmed	Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat
title_sort	rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against cums-induced depression-like behaviors in adolescent rat
publisher	BMC
publishDate	2021
url	https://doaj.org/article/0489f7a364a84c49a2374c71294d9e43
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Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat

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