Aged microbiota exacerbates cardiac failure by PPARα/PGC1α pathway

Abstract

The dysbiosis of gut microbiota with aging has been extensively studied, revealing its substantial contribution to variety of diseases. However, the impact of aged microbiota in heart failure (HF) remains unclear. In this study, we employed the method of fecal microbiota transplantation (FMT) from aged donors to investigate its role in the context of HF. Our results demonstrate that FMT from aged donors alters the recipient's gut microbiota composition and abundance. Furthermore, FMT impairs cardiac function and physical activity in HF mice. Aged FMT induces metabolic alterations, leading to body weight gain, impaired glucose tolerance, increased respiratory exchange ratio, and enhanced fat accumulation. The epicardium of aged FMT recipients shows fat accumulation, accompanied by cardiomyocyte hypertrophy, cardiac fibrosis and increased cellular apoptosis. Mechanistically, aged FMT suppresses the PPARα/PGC1α signaling pathway in HF. Notably, activation of PPARα effectively rescues the metabolic changes and myocardial injury caused by aged FMT. In conclusion, our study emphasizes the role of the PPARα/PGC1α signaling pathway in aged FMT-mediated HF.