AUTHOR=Cui Xialian , Su Yangyan , Huang Xiaotong , Chen Jiaping , Ma Jiang , Liao Peiran , He Xin 

TITLE=Combined analysis of plasma metabolome and intestinal microbiome sequencing to explore jiashen prescription and its potential role in changing intestine–heart axis and effect on chronic heart failure

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1147438

DOI=10.3389/fcvm.2023.1147438

ISSN=2297-055X

ABSTRACT=Heart failure (HF) is a chronic progressive disease, which is a complex clinical syndrome caused by impaired cardiac structure or function, and then impaired ventricular filling or ejection capacity. Its high morbidity and mortality threaten human health. Jiashen Prescription (JSP), a traditional Chinese medicine (TCM) formula, could be significantly improve the symptoms of HF. In order to reveal the potential mechanism of JSP in treating heart failure, a heart failure model in SD rats were established who were treated with JSP by gavage. In this study, plasma and intestinal contents of rats from Control group, HF Model group and JSP administration group were collected. Then the untargeted metabolomics of plasma and intestinal microbial 16S rRNA sequences of rats were determined. Combined with the results of fuzzy c-means clustering and functional clustering analysis of metabolite content, 8 plasma metabolites with potential functions under the trend of two changes (Cluster 2 and Cluster 3&6) were obtained. Through the conjoint analysis of 8 metabolites and the OTUs relative abundance data in the 16S rRNA sequencing results by WGCNA method, 215 floras significantly related to the 8 compounds were identified. It was shown that JSP could improve the cardiac function of heart failure rats and thus ameliorate heart failure via enhancing LVEF of rats. Results of intestinal flora analysis revealed that JSP adjusted gut microbiota disturbances by reducing the abundance of pathogenic bacteria, such as Allobaculum, Brevinema, increasing the abundance of beneficial bacteria, including Lactobacillus, Lachnospiraceae_NK4A136_group and so on. JSP improved metabolic disorders by reversing metabolite plasma levels to normality. The results of the correlation analysis demonstrated a significant association between intestinal microbiota and plasma metabolic profile, especially the significant correlation of Ruminococcaceae_UCG-014 and Protoporphyrin IX, Ruminococcaceae_UCG-005, Christensenellaceae_R-7_group and nicotinamide, dihydrofolic acid. This study illustrated the underlying mechanism of JSP to treat HF by affected intestinal flora and plasma metabolites and was provided a potential therapeutic strategy against HF.