Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in chronic heart failure patients

Xiao Cui,Ling Jin,Lifeng Li,Shouling Wu,Wenjie Wang,Lei Ye,Shuangyue Li,Jing Li,Bin Geng,Minghui Bao,Jun Cai,Xin Zhou,Jian Zhang

doi:10.1038/s41598-017-18756-2

Abstract

Previous studies suggested a possible gut microbiota dysbiosis in chronic heart failure (CHF). However, direct evidence was lacking. In this study, we investigated the composition and metabolic patterns of gut microbiota in CHF patients to provide direct evidence and comprehensive understanding of gut microbiota dysbiosis in CHF. We enrolled 53 CHF patients and 41 controls. Metagenomic analyses of faecal samples and metabolomic analyses of faecal and plasma samples were then performed. We found that the composition of gut microbiota in CHF was significantly different from controls. Faecalibacterium prausnitzii decrease and Ruminococcus gnavus increase were the essential characteristics in CHF patients’ gut microbiota. We also observed an imbalance of gut microbes involved in the metabolism of protective metabolites such as butyrate and harmful metabolites such as trimethylamine N-oxide in CHF patients. Metabolic features of both faecal and plasma samples from CHF patients also significantly changed. Moreover, alterations in faecal and plasma metabolic patterns correlated with gut microbiota dysbiosis in CHF. Taken together, we found that CHF was associated with distinct gut microbiota dysbiosis and pinpointed the specific core bacteria imbalance in CHF, along with correlations between changes in certain metabolites and gut microbes.

Highlights

Chronic heart failure (CHF) is an end-stage syndrome of many cardiovascular diseases, associated with structural and/or functional abnormalities of heart, leading to insufficient blood perfusion to meet the body’s requirements[1]
The majority of chronic heart failure (CHF) patients were with poor cardiac function that 51% of them were in the New York Heart Association functional classification (NYHA) III; 43% in NYHA IV, 6% in NYHA II and none in NYHA I
None of the subjects had inflammatory bowel diseases, irritable bowel syndrome, autoimmune diseases, liver diseases, renal diseases or cancer, but more CHF patients were comorbid with hypertension, hyperlipidaemia and diabetes compared with controls

Summary

Introduction

Chronic heart failure (CHF) is an end-stage syndrome of many cardiovascular diseases, associated with structural and/or functional abnormalities of heart, leading to insufficient blood perfusion to meet the body’s requirements[1]. A recent study showed that dietary intervention could prevent the development hypertension and heart failure in hypertensive mice through changing their gut microbiota[12]. Whether gut microbiota dysbiosis could contribute to CHF through triggering systematic inflammation as well as producing trimethylamine N-oxide (TMAO) and some other uremic toxins www.nature.com/scientificreports/. Studies have shown that levels of TMAO, a gut microbes-dependent metabolite, elevated and showed predictive value for poor prognosis in studies on both chronic and acute heart failure patients[14]. Direct evidence for gut microbiota dysbiosis in CHF patients was still lacking. We performed metagenomic analyses of faecal samples from CHF patients, in combination with faecal and plasma metabolomic analyses, to provide direct evidence and comprehensive understanding of gut microbiota dysbiosis in CHF

Methods

Results

Conclusion