Insights into the associations between the gut microbiome, its metabolites and heart failure.

Abstract

Heart failure (HF) is the end stage of most cardiovascular diseases and remains a significant health problem globally. We aimed to assess whether patients with left ventricular ejection fraction ≤45% had alterations in both the gut microbiome profile and production of associated metabolites when compared to a healthy cohort. We also examined the associated inflammatory, metabolomic, and lipidomic profiles of HF patients. This single centre, observational study, recruited 73 HF patients and 59 healthy volunteers. Blood and stool samples were collected at baseline and 6-month follow-up, along with anthropometric and clinical data. Compared to healthy controls, HF patients had reduced gut bacterial alpha diversity at follow-up (p =0.004) but not at baseline. The stool microbiota of HF patients was characterized by a depletion of operational taxonomic units representing commensal Clostridia at both baseline and follow-up. HF patients also had significantly elevated baseline plasma acetate (p =0.007), plasma TMAO (p =0.003), serum sCD14 (p =0.005) and sCD163 (p =0.004) levels compared to healthy controls. Furthermore, HF patients had a distinct metabolomic and lipidomic profile at baseline when compared to healthy controls. Differences in the composition of the gut microbiome and the levels of associated metabolites were observed in patients with HF when compared to a healthy cohort. This was also associated with an altered metabolomic and lipidomic profile. Our study identifies microorganisms and metabolites that could represent new therapeutic targets and diagnostic tools in the pathogenesis of HF.