AUTHOR=Zhang Zhendong , Cai Bin , Sun Yanzhuan , Deng Haiyan , Wang Hongwei , Qiao Zengyong TITLE=Alteration of the gut microbiota and metabolite phenylacetylglutamine in patients with severe chronic heart failure JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=Volume 9 - 2022 YEAR=2023 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1076806 DOI=10.3389/fcvm.2022.1076806 ISSN=2297-055X ABSTRACT=Chronic Heart Failure (CHF) is the end result of almost all forms of cardiovascular disease and remains the leading cause of death worldwide. Numerous studies have demonstrated that the intestinal flora plays an important role in the development and progression of cardiovascular disease, prompting new ideas for disease diagnosis and treatment. Phenylacetylglutamine (PAGln) is one of the common chronic kidney disease toxins, and patients with Major Adverse Cardiovascular Events have been shown to have high plasma PAGln concentrations. However, its variation in patients with different levels of CHF has rarely been reported. Therefore, we collected stool and plasma samples from 22 healthy controls, 29 New York Heart Association (NYHA) class III, and 29 NYHA class IV CHF patients, and conducted bacterial 16S ribosomal RNA gene sequencing and liquid chromatography tandem mass spectrometry. There were many significant differences between the two groups. Firstly, the Chao 1 index was significantly lower in both NYHA class III and NYHA class IV than that in the control group. The beta diversity was significantly different among the three groups. Additionally, the linear discriminant analysis effect size analysis revealed that the most different groups in the control group, NYHA class III, and NYHA class IV were Lachnospiraceae, Enterobacteriaceae, and Escherichia. Secondly, the plasma PAGln levels were significantly higher in the NYHA class III and NYHA class IV patients than those in the control group, and the PAGln levels were significantly higher in the NYHA class IV patients than those in NYHA class III. Finally, the correlation analysis showed that Parabacteroides and Bacteroides were negatively correlated with brain natriuretic peptide (BNP) and PAGln, and Romboutsia and Blautia were negatively correlated with PAGln. Klebsiella was positively correlated with BNP and Escherichia-Shigella was positively correlated with BNP and PAGln. Then, Alistipes was negatively correlated with BNP, and Parabacteroides was negatively correlated with the left ventricular end-diastolic diameter. This study showed that the intestinal flora and metabolite PAGln were altered with different degrees of CHF and explored the effects of the intestinal flora and its metabolites on CHF.