Alterations of the Gut Microbiota in Patients With Severe Chronic Heart Failure

Abstract

Chronic heart failure (CHF) is the final outcome of almost all forms of cardiovascular diseases, remaining the main cause of mortality worldwide. Accumulating evidence is focused on the roles of gut microbial community in cardiovascular disease, but few studies have unveiled the alterations and further directions of gut microbiota in severe CHF patients. Aimed to investigate this deficiency, fecal samples from 29 CHF patients diagnosed with NYHA Class III-IV and 30 healthy controls were collected and then analyzed using bacterial 16S rRNA gene sequencing. As a result, there were many significant differences between the two groups. Firstly, the phylum Firmicutes was found to be remarkably decreased in severe CHF patients, and the phylum Proteobacteria was the second most abundant phyla in severe CHF patients instead of phylum Bacteroides strangely. Secondly, the α diversity indices such as chao1, PD-whole-tree and Shannon indices were significantly decreased in the severe CHF versus the control group, as well as the notable difference in β-diversity between the two groups. Thirdly, our result revealed a remarkable decrease in the abundance of the short-chain fatty acids (SCFA)-producing bacteria including genera Ruminococcaceae UCG-004, Ruminococcaceae UCG-002, Lachnospiraceae FCS020 group, Dialister and the increased abundance of the genera in Enterococcus and Enterococcaceae with an increased production of lactic acid. Finally, the alternation of the gut microbiota was presumably associated with the function including Cell cycle control, cell division, chromosome partitioning, Amino acid transport and metabolism and Carbohydrate transport and metabolism through SCFA pathway. Our findings provide the direction and theoretical knowledge for the regulation of gut flora in the treatment of severe CHF.

Keywords: 16S rRNA gene; SCFA; gut microbiota; patients; severe chronic heart failure.

FIGURE 1

The distribution of relative abundance in the CHF and the healthy control group. Panel (A) shows the distribution of relative abundance of top 19 at phylum level in the two groups. Panel (B) shows the distribution of relative abundance at the genus level in the two groups. HF, CHF group; CON, the healthy control group.

FIGURE 2

The α-diversity indices and the β-diversity of the gut microflora between the CHF group and the healthy control group. (A) PD-whole tree indice; (B) Chao1 indices; (C) Shannon indices; (D) β-diversity based on the weighted UniFrac. HF, CHF group; CON, the healthy control group.

FIGURE 3

The results of differential taxonomy expression analysis using limma algorithm. Panel (A) shows the differential taxonomy expression in the CHF patients vs. healthy control group; (B) shows the differential taxonomy expression in every samples.

FIGURE 4

The results of PICRUst based on closed-reference OTU to predict the abundances of functional categories COG orthologs (COs) and KEGG orthologs (KOs). Panels (A,C) shows the KOs with significantly different abundances in the fecal microbiome between the CHF group and healthy control group; (B,D) shows the COs with significantly different abundances in the fecal microbiome between the CHF group and healthy control group. HF, CHF group; CON, the healthy control group.