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

Journal of Neuroinflammation

Yujiao Xiang¹  Zemeng Zhu²  Zhijun Jiang²  Dexiang Liu²  Haonan Li²  Wei Wang²  Fang Pan²  Shuyue Cheng²  Mingyue Zhao²  Cyrus S. H. Ho³  Roger C. M. Ho⁴ 

[1] Cheeloo Hospital, Shandong University, Jinan, People’s Republic of China;Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China;Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;Institute of Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore;

关键词: Adolescence;    Chronic unpredictable mild stress (CUMS);    Rifaximin;    Gut microbiome;    Short chain fatty acid (SCFA);    Microglia;    Neurogenesis;   

DOI  :  10.1186/s12974-021-02303-y

来源: Springer

【 摘 要 】

BackgroundChronic 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.MethodsWe 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.ResultsOur 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.ConclusionsThese 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.

【 授权许可】

CC BY