The Gut Microbiota and Metabolites in HFpEF

Condition(s) studied

Study summary

Heart failure (HF) with preserved ejection fraction (HFpEF) has emerged as a critical public health concern. The annual mortality rate for HFpEF is approximately 15%, accompanied by a re-hospitalization rate of nearly 80%. Survival rates over a 5-year period typically range from 25% to 50%. Existing medications effective against HF with reduced ejection fraction (HFrEF) have shown no significant effect on HFpEF. Only the sodium-glucose cotransporter 2 inhibitor (SGLT2i) has demonstrated significant improvements in patient survival and re-hospitalization rates, thus earning a Class IA recommendation in clinical guidelines. HFpEF is characterized as a complex, heterogeneous, multi-organ systemic syndrome primarily associated with risk factors such as advanced age, obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM), hypertension, sedentary lifestyle, coronary atrial disease (CAD), and kidney disease. Therefore, it is crucial to investigate other multi-system disorders closely associated with cardiac diastolic dysfunction to gain a comprehensive understanding of the underlying mechanisms of HFpEF. The human digestive tract harbors a complex and dynamic microbial community known as the gut microbiota, which comprises up to 100 trillion microorganisms and approximately 150 times more genomes than the human genome, often referred to as the "second genome" of the human body. Recent years have seen growing recognition and extensive research into the role of gut microbiota in the pathogenesis and development of cardiovascular diseases. In HFrEF patients, there is a significant decrease in the diversity of gut microbiota, along with changes in its composition and structure. Notably, pathogenic bacteria such as Campylobacter and Candida species exhibit a substantial increase correlating with disease severity, while anti-inflammatory bacteria like Brauteria demonstrate a marked decrease. Furthermore, gut microbiota can influence the host's cardiometabolic traits through the modulation of both its own and host-produced metabolites. HFpEF is increasingly considered a metabolic disease. Comorbidities associated with HFpEF, including obesity, T2DM, metabolic syndrome, hypertension, and coronary artery disease (CAD), have been reported to be closely related to gut microbiota. However, the relationship between gut microbiota and HFpEF is still not fully understood. A recent study indicates that indole-3-propionic acid (IPA) could attenuate diastolic and metabolic dysfunction and mitigate gut microbiota dysbiosis in an HFpEF mouse model. Several clinical studies have noted alterations in microbial metabolites such as short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO) in HFpEF patients. It is now well recognized that targeting the gut microbiome and its metabolites represents a promising novel therapeutic strategy for managing cardiovascular diseases. Therefore, this study is to investigate the changes and function of gut microbiota and metabolites in HFpEF.

Eligibility

Primary outcome measure(s)

• Death and rehospitalization — 3 years
  All-cause death and rehospitalization due to cardiac causes within 3 years

Trial sites (1)

More The First Affiliated Hospital with Nanjing Medical University trials in China

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