Gut microbiome shifts in chronic systolic heart failure are associated with disease severity and clinical improvement

Chronic systolic heart failure (HF) is a prevalent and morbid disease with marked variability in its progression and response to therapies. The gut microbiome may play a role in pathophysiology and progression of chronic HF, but clinical studies investigating relationships between the two are lacking. We analyzed the gut microbiome in a cohort of adults with chronic systolic HF caused by non-ischemic cardiomyopathy (n=59) using multi-omics profiling and, in some cases, longitudinal sampling. We identified microbiome differences compared to healthy subjects (n=50) and associated these differences with host metabolites, inflammatory markers and physiology. We found depletion of the anti-inflammatory probiotic Bifidobacterium and the associated short chain fatty acid producing and formaldehyde detoxifying pathways in the chronic HF cohort. We also discovered HF-specific microbiome-host immunome interactions. In addition to identifying several taxa and microbial pathways broadly associated with HF disease severity, we found significant links between Bifidobacterium and clinical HF improvement over time. Gut microbiome-host multi-omic data integration revealed a close association between Bifidobacterium and circulating metabolites previously implicated in cardiovascular physiology (e.g., malonic acid), thus pointing to potential mechanisms through which Bifidobacterium may affect chronic HF physiology. Our results suggest that Bifidobacterium may serve as a biomarker for chronic HF trajectory as well as suggest potential novel therapeutic interventions strategies.