AUTHOR=Liang Xing-Qiu , Mai Peng-Yu , Qin Hui , Li Sen , Ou Wen-Juan , Liang Jian , Zhong Jing , Liang Ming-Kun 

TITLE=Integrated 16S rRNA sequencing and metabolomics analysis to investigate the antidepressant role of Yang-Xin-Jie-Yu decoction on microbe-gut-metabolite in chronic unpredictable mild stress-induced depression rat model

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.972351

DOI=10.3389/fphar.2022.972351

ISSN=1663-9812

ABSTRACT=Objectives: Our goals were to evaluate the antidepressant efficacy of Yang-Xin-Jie-Yu Decoction (YXJYD) in Chronic Unpredictable Mild Stress (CUMS)-induced depression rat model and to investigate the underlying mechanisms.
Design:  We used CUMS-induced depression rat model to evaluate whether oral administration of YXJYD with different doses (2.1g/kg, 1.05g/kg and 0.525g/kg, respectively) improve the depressive-like symptoms, and then performed UHPLC-Q-TOF-MS to explore the active ingredients of YXJYD. Subsequently, rat’s cecal contents, serum, and urine were collected from the control group, CUMS model group, and YXJYD high-dose (2.1g/kg) treatment group. The 16S rRNA sequencing was performed on the cecal contents, based on Illumina MiSeq platform, and ANOVA analysis were used to analyze the composition variety and screen differential expression of gut bacteria in the three groups. 1H Nuclear Magnetic Resonance (NMR) analysis was used for analyzing the metabolites obtained from cecal contents, serum, and urine, and KEGG enrichment analysis was used to identify pathways of differential metabolites. An integrated 16S rRNA sequencing and metabolomic data were conducted to characterize the underlying mechanisms of YXJYD . 
Results: We found that the abundance of Monoglobus was the most relevant gut microbe that associated with YXJYD improved depressive-like symptoms in CUMS model rats. With an integrated study of the gut microbiota and metabolomes, we identified the  pathway of tricarboxylic acid cycle(TCA cycle) and propanoate metabolism as the regulated target of YXJYD on host-microbiome interaction. In the TCA cycle and propanoate metabolism, there were four and five enzymes were identified to be associated with YXJYD-treatment, respectively. 
Conclusion: In conclusion, our findings further confirmed that the imbalance of metabolism and intestinal microbial is closely related to CUMS-induced depression, and YXJYD can improve the metabolic disorder of CUMS-induced depression by regulating the gut microbiome and body metabolomes.