Gut microbiome-derived metabolites as prognostic biomarkers in heart failure: a systematic review and meta-analysis
Abstract
With growing evidence implicating gut dysbiosis in the initiation and progression of heart failure, microbial metabolites hold promise as novel prognostic biomarkers and therapeutic targets.
This systematic review and meta-analysis summarises the prognostic utility of gut microbial metabolites, namely trimethylamine-N-oxide (TMAO), phenylacetylglutamine (PAGln), indoxyl sulfate, imidazole propionate and short-chain fatty acids (SCFAs), across different phenotypes of heart failure.
Medline, Embase, Cochrane Library, Web of Science and Google Scholar were systematically searched through February 2025 for non-randomised diagnostic studies investigating the association between gut microbial metabolites and clinical outcomes in heart failure. Prespecified study characteristics, baseline covariates and outcome data were extracted by two independent, blinded reviewers. The prespecified primary outcome was all-cause mortality, prespecified secondary outcomes were cardiovascular mortality and major adverse cardiac events (MACE). Random-effect models were applied to pool hazard ratios (HR) and 95% confidence intervals (CI). Subgroup analysis was performed with respect to heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF), and ischaemic (ICM) or non-ischaemic cardiomyopathy (NIDCM). This study was registered on PROSPERO.
Following screening of 2991 abstracts, 19 studies comprising 17484 patients were included in meta-analysis; a further 6 studies were synthesised…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 17,484 participants or records.
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