Xin-Ji-Er-Kang alleviates heart failure induced by myocardial ischemia-reperfusion injury through reshaping gut microbiota and metabolites.

Abstract

BACKGROUND: The relationship between the gut-heart axis and heart failure has attracted growing interest, making the gut microbiota a potential target for new treatments. Previously, we have reported the beneficial effects of the traditional Chinese medicine Xin-Ji-Er-Kang (XJEK) on heart failure (HF), but the influence of the intestinal microbiota on XJEK's protection of the heart remains to be confirmed. PURPOSE: This study investigates the role of gut microbiota in XJEK's therapeutic impact on HF and elucidates its potential mechanism. STUDY DESIGN: MIR-induced HF model mice were established and different concentrations of XJEK were administered by gavage. The pharmacological effects of XJEK were evaluated by multiple pharmacodynamic methods. Subsequently, fecal microbiota transplantation (FMT) and antibiotic-induced microbiota inhibition were used to explore the effect of XJEK on HF. We next employed 16S rRNA sequencing combined with fecal metabolomics to investigate alterations in gut microbiota and metabolic profiles, and further investigated the effects of mono-colonization with D. piger in mice. RESULTS: XJEK administration dose-dependently enhanced cardiac function and reduced myocardial damage in MIR-induced HF mice, as evidenced by reduced cardiomyocyte hypertrophy, diminished myocardial fibrosis, and a decline in serum levels of NT-proBNP and cTnI. FMT from XJEK-treated mice to recipient mice revealed that the therapeutic effects of XJEK on heart failure partially depend on the gut microbiota. XJEK reshaped the gut microbiota, leading to elevated abundance of probiotics Faecalibacterium, Limosilactobacillus and Bifidobacterium, while pathogenic bacteria Staphylococcus was depleted. Additionally, XJEK elevated the levels of beneficial metabolites, including deoxycholic acid and β-MCA. Notably, XJEK led to a rise in the relative abundance of D. fairfieldensis, and through the study of D. piger of the same genus, it was found that Desulfovibrio may produce beneficial effects in HF mice. CONCLUSION: XJEK effectively improved cardiac function, mitigated myocardial injury, and suppressed the progression of heart failure. XJEK improved gut microbiota composition and related metabolism, alleviating heart failure.