Systolic heart failure, gut microbiome, multi-omics dataset

Chronic systolic heart failure (HF) is a prevalent and morbid disease with marked variability in its progression and response to therapies. The gut microbiome has been hypothesized to contribute to HF pathophysiology, but clinical studies exploring potential relationships are limited.Our study objective was to investigate gut microbiome alterations in chronic systolic HF and their associations with host metabolites, immune responses, and disease severity using multi-omics profiling.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 (including microbiome metagenomics, cytokine profiling, untargeted metabolomics, targeted lipidomics, and targeted microbial metabolite profiling) and, in some cases, longitudinal sampling. Comparisons were made with healthy subjects (n=50) and associations with metabolites, inflammatory markers, and HF severity were evaluated.We found that the anti-inflammatory probiotic Bifidobacterium and the associated short chain fatty acid-producing metabolic pathways were depleted 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 identified significant associations between Bifidobacterium and clinical HF improvement over time. Gut microbiome-host multi-omic data integration revealed a close association between Bifidobacterium and the circulating metabolite indole-3-propionic acid, which was previously implicated in cardiovascular physiology, pointing to potential mechanisms through which Bifidobacterium may affect chronic HF physiology.Our findings reveal profound gut microbiome shifts in chronic systolic HF with potential systemic host effects. We also identify Bifidobacterium as a potential biomarker for chronic HF trajectory and suggest novel microbiome-based therapeutic strategies.