Gut Microbiota Dysbiosis and Metabolite Pathways in Heart Failure: A Systematic Review

The gut microbiome plays a critical role in heart failure (HF) through immune, metabolic, and inflammatory pathways. Altered microbial composition and metabolites may contribute to HF pathogenesis and progression. This systematic review compared gut microbiome profiles in adults with HF and healthy controls (HCs), highlighted microbial taxa linked to HF incidence, and examined functional and metabolic pathway changes. Eligible studies included peer-reviewed research comparing gut microbiota in adults with HF and HCs reporting taxonomic, functional, or metabolite outcomes. A systematic search of PubMed, Scopus, and Web of Science identified studies published between January 2021 and August 2025. Data extraction used a structured table to capture study characteristics, while quality was assessed with the Newcastle–Ottawa Scale. Ten studies involving 407 HF patients and 327 HCs were reviewed. Heart failure patients showed reduced microbial richness and diversity compared with healthy controls. Depletion of beneficial short-chain fatty acid (SCFA) producing taxa such as Firmicutes (Faecalibacterium, Ruminococcaceae, Lachnospiraceae) and Actinobacteria (Bifidobacterium) was common, while enrichment of opportunistic Proteobacteria (Klebsiella, Escherichia, Enterobacteriaceae) was reported. Functional analyses highlighted downregulation of butyrate- and propionate-producing pathways and increased pro-inflammatory metabolites production, particularly trimethylamine N-oxide (TMAO). Subtype differences were suggested between HFrEF and HFpEF, though HFmrEF was not examined. Limitations included methodological heterogeneity, lack of longitudinal designs, and restriction to English-language studies. HF is consistently associated with gut dysbiosis, marked by loss of SCFA-producing commensals and enrichment of pathogenic taxa with harmful metabolic potential. Broader, longitudinal, and subtype-specific studies required to establish causality and guide microbiota-targeted therapies in HF.