Aged microbiota exacerbates cardiac failure by PPARα/PGC1α pathway

Area of Science:

• Microbiology
• Cardiology
• Gerontology

Background:

• Gut microbiota dysbiosis is linked to aging and various diseases.
• The specific role of aged gut microbiota in heart failure (HF) is not well understood.

Purpose of the Study:

• To investigate the impact of fecal microbiota transplantation (FMT) from aged donors on heart failure progression.
• To elucidate the underlying mechanisms, focusing on metabolic alterations and signaling pathways.

Main Methods:

• Fecal microbiota transplantation (FMT) from aged donors to HF mice.
• Assessment of cardiac function, physical activity, metabolic parameters, and cardiac histology.
• Analysis of the PPARα/PGC1α signaling pathway.

Main Results:

• Aged FMT altered gut microbiota composition and impaired cardiac function and physical activity in HF mice.
• Aged FMT induced metabolic dysfunction, including weight gain, impaired glucose tolerance, and increased fat accumulation.
• Aged FMT led to epicardial fat accumulation, cardiomyocyte hypertrophy, fibrosis, apoptosis, and suppressed PPARα/PGC1α signaling.

Conclusions:

• Aged gut microbiota exacerbates heart failure through metabolic dysregulation and cardiac injury.
• The PPARα/PGC1α signaling pathway is a key mediator in aged FMT-induced heart failure.
• Activating PPARα can ameliorate the adverse effects of aged FMT on metabolism and cardiac health.