A multi-omic study published in Nature Cardiovascular Research links gut microbiome shifts, microbial metabolites, and changes in heart function in patients with chronic systolic heart failure due to nonischemic cardiomyopathy. Researchers found that specific bacterial populations and metabolic pathways correlate with disease severity and clinical improvement, opening new avenues for understanding heart failure progression.
Gut Microbiome Composition in Chronic Systolic Heart Failure
Researchers combined metagenomic sequencing, metabolomics, and gene set enrichment analysis to evaluate 59 adults with chronic systolic heart failure due to nonischemic cardiomyopathy and 50 healthy participants from the integrated Personal Omics Profiling study. The heart failure patients were enrolled between July 2018 and March 2020. The analysis revealed that alpha diversity and anti-inflammatory microbes were depleted in the guts of heart failure patients.
Specifically, patients showed lower levels of the Lachnospiraceae family and the genera Anaerobutyricum, Anaerostipes, Blautia, and Lachnospira compared to healthy controls. At the same time, pro-inflammatory genera such as Prevotella and Sutterella were enriched in the heart failure group. Functional profiling indicated that pathways associated with short-chain fatty acid production, methane production, L-arginine production, and formaldehyde detoxification were downregulated, while pathways involved in pro-inflammatory lipopolysaccharide generation were enriched.
Bifidobacterium Abundance and Microbial Metabolites
The study identified specific microbial signatures associated with milder disease measures and improved functional status. Greater abundance of Bifidobacterium—certain strains of which produced indole-3-propionic acid in laboratory experiments—correlated with milder disease and better functional status. Furthermore, higher circulating indole-3-propionic acid and predicted microbial butyrate production aligned with milder heart failure measures.
Altered L-arginine and ornithine pathways in the study cohort linked to different microbiome-immune interactions. These pathways participate in gut barrier function, inflammation, and the production of nitric oxide and polyamines, though the study did not establish that shifts in the microbiome directly altered their systemic production.
Longitudinal Tracking of Clinical Outcomes
To assess changes over time, the research team performed longitudinal analyses on a subset of the cohort. Twenty-six heart failure patients returned for repeat multi-omic profiling and clinical assessment after an average of six months. Longer-term clinical follow-up data were obtained for 51 patients after an average of 27 months.
Clinical outcomes were tracked based on heart transplantation, left ventricular assist device placement, hospice care, or death. Clinical improvement was measured using the Kansas City Cardiomyopathy Questionnaire, New York Heart Association functional classes, and left ventricular ejection fraction. For the six-month analysis, improvement required a decrease of at least one New York Heart Association class, a left ventricular ejection fraction increase of at least 5%, or a Kansas City Cardiomyopathy Questionnaire overall summary score increase of at least five points. Machine learning integration of laboratory, cytokine, microbiota, and microbial pathway data successfully distinguished heart failure patients from healthy individuals.
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