Abstract Body:
Background: Heart failure (HF) has been associated with dysregulated gut microbiome. However, less is understood about how gut microbiome alterations relate to changes in HF severity. We sought to understand how gut microbial shifts and associated host signatures related to changes in clinical status of patients with HF with reduced ejection fraction (HFrEF).
Methods: Twenty-six adults with HFrEF were recruited and completed 2 study visits approximately 6 months apart. At each visit they provided stool sample for microbiome profiling (metagenomic sequencing), and fasting blood samples for untargeted metabolomics (liquid chromatography–mass spectrometry) and cytokine assay (Luminex antibody-conjugated bead capture). Subjects also completed dietary surveys. Clinical improvement was measured as between-visit change in the New York Heart Association (NYHA) class.
Results: Between-visit NYHA class improved in 6 individuals; 20 patients remained stable or worsened. After accounting for demographics, body mass index, and diet, genus Bifidobacterium was significantly enriched in the improved group and increased over time (Figure 1). Bifidobacterium was directly associated with circulating malonic acid, which is implicated in cardio-protection and cardiomyocyte regeneration, and with indole-3-propionate (IPA), anti-inflammatory gut microbial metabolite of dietary tryptophan (Figure 2). There was also a positive correlation between Bifidobacterium and IL10, a major anti-inflammatory cytokine that plays a role in cardiac remodeling.
Conclusion: Bifidobacterium was independently associated with longitudinal improvement in functional status in patients with HFrEF. Additionally, Bifidobacterium correlated with circulating IPA, malonic acid, and IL10. Our findings support (1) gut Bifidobacterium as a potential biomarker of clinical improvement in HFrEF and a possible new therapeutic target, and (2) potential downstream mediators through which Bifidobacterium may regulate HF pathophysiology.