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Open AccessArticle

Gut Microbiota is the Key to the Antidepressant Effect of Chaihu-Shu-Gan-San

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China
Author to whom correspondence should be addressed.
Metabolites 2020, 10(2), 63;
Received: 7 December 2019 / Revised: 15 January 2020 / Accepted: 25 January 2020 / Published: 10 February 2020
(This article belongs to the Special Issue Gut Metabolism of Natural Products)
Accumulating evidence highlights the link between gut microbiota and depression. As an antidepressant herbal drug in clinic, Chaihu-Shu-Gan-San (CSGS) has also been used in China for the treatment of various gastrointestinal disorders. Therefore, we hypothesize that the gut microbiota might be involved in the effect of CSGS. Here, we investigated the antidepressant effects of CSGS against chronic variable stress (CVS)-induced depression rats with and without antibiotic treatment using 16S rRNA gene sequencing and ultra-performance liquid chromatography coupled with time of flight mass spectrometry (UPLC-Q-TOF/MS) based metabolome approaches. As a result, the prominent effects of CSGS against the depression-like behavioral disorder of CVS-induced rats were significantly weakened when the gut microbiota was changed after oral administration of the broad-spectrum antibiotic. The mediation of CSGS on hippocampal levels of serotonin (5-HT) and glutamic acid (Glu) was also receded with the antibiotic treatment. Further investigation on the diversity of microbiome indicated that the improvement effect of CSGS on gut microbiota dysbiosis—especially the phylum level of Firmicutes—was attenuated compared with the CSGS combined antibiotic treated one. Moreover, 3-hydroxypicolinic acid (H4) and inosine (H8) in the hippocampus were considered as important biomarkers for depression and are also associated with gut microbiota mediated CSGS efficacy. Taken together, our current study indicated that gut microbiota is a critical factor in the antidepressant effect of CSGS, and this acts in part through gut microbiota to improve depression-related biomarkers.
Keywords: CSGS; antidepressant; antibiotic treatment; gut microbiota; metabolomics CSGS; antidepressant; antibiotic treatment; gut microbiota; metabolomics
MDPI and ACS Style

Yu, M.; Jia, H.-M.; Zhang, T.; Shang, H.; Zhang, H.-W.; Ma, L.-Y.; Zou, Z.-M. Gut Microbiota is the Key to the Antidepressant Effect of Chaihu-Shu-Gan-San. Metabolites 2020, 10, 63.

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