Bacteroides vulgatus alleviates heart failure via butyric acid-TGF-β1/MAPK pathway

Abstract

Introduction

The gut microbiota plays a vital role in the progression of heart failure (HF), making it a potential strategy for treating HF. The Bacteroides genus has shown promising potential for treating HF. However, further research is needed to identify specific beneficial Bacteroides strains for treating HF and elucidate their potential mechanisms.

Objectives

This study aimed to elucidate the therapeutic effect and mechanism of Bacteroides strain on HF.

Methods

This study comprehensively used pharmacological evaluation, 16S rRNA genetic sequencing, SCFA targeted metabolomics, transcriptome, and molecular biology methods to investigate the efficacy and mechanism of Bacteroides vulgatus (B. vulgatus) in the treatment of HF.

Results

We observed a significant decrease in the abundance of B. vulgatus in both HF patients and mice, and dysbiosis of the gut microbiota could cause cardiac dysfunction in mice. The administration of B. vulgatus to mice with HF significantly improved their cardiac function and significantly increased the levels of SCFAs, especially butyric acid. Meanwhile, we also observed a significant reduction in the levels of butyric acid in the serum of HF patients, and the cardiac function of HF mice improved after the administration of butyric acid. Compared to patients with higher butyric acid level, patients with lower butyric acid level had a significantly increased incidence of endpoint events. Moreover, the transcriptome results revealed that B. vulgatus significantly regulated the mitogen-activated protein kinase (MAPK) pathway. After further molecular biology verification, B. vulgatus was confirmed to regulate the TGF-β1/MAPK pathway in the heart through butyric acid, thereby exerting anti-HF effects.

Conclusion

This study provides evidence that B. vulgatus improves heart function by regulating SCFA metabolism and subsequently modulating the TGF-β1/MAPK pathway in myocardial tissue, confirming the potential therapeutic role of B. vulgatus in HF.