Abstract
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 metabolomics 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 after the CSGS combined antibiotic treatment. 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, which improve depression-related metabolic disturbance partly through gut microbiota.
Highlights
Depression is a range of neuro-behavioral disorders characterized by anhedonia, depressed mood, and high suicide rates [1,2]
Our recent study showed that the gut microbiota composition altered in chronic variable stress (CVS)-induced depression rats, in particular, two major phyla bacteria; the abundance of Firmicutes was reduced while the abundance of Bacteroidetes was increased, which was in line with other research findings in depressed patients [6,7]
An integrated gut microbiome and metabolomic approach was performed to explore the impact of gut microbiota on the antidepressant effect of CSGS with and without antibiotic treatment
Summary
Depression is a range of neuro-behavioral disorders characterized by anhedonia, depressed mood, and high suicide rates [1,2]. The pathohistological hallmark of depression is neurotransmission decrease, hypothalamic–pituitary–adrenal (HPA) axis alterations, and immune system abnormalities [3]. Our recent study showed that the gut microbiota composition altered in chronic variable stress (CVS)-induced depression rats, in particular, two major phyla bacteria; the abundance of Firmicutes was reduced while the abundance of Bacteroidetes was increased, which was in line with other research findings in depressed patients [6,7]. We found that 11 genera bacteria were altered under the depression condition [7]. Taken together, these studies indicate that gut microbiota may causatively
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