New insights into the gut-heart axis: microbial metabolite biomarkers, multi-omics, and engineered bacterial delivery systems.

Abstract

Despite rapid growth in gut-heart axis research, clinical translation remains limited. This review addresses that gap by critically synthesizing recent evidence on microbiota-derived metabolites, biomarkers, multi-omics workflows, and engineered bacterial interventions in cardiovascular disease (CVD). We examine how TMAO, short-chain fatty acids, bile acids, indole derivatives, and phenylacetylglutamine exert context-dependent cardiovascular effects, and why functional microbial gene markers and integrated biomarker panels may outperform single-taxon signatures. We then evaluate multi-omics strategies, metagenomics, metabolomics, proteomics, single-cell and spatial omics, and bioinformatics integration, for causal inference and biomarker validation. Finally, we assess engineered bacterial delivery systems, including gene circuit design, colonization control, biocontainment, and safety, and outline short-, medium-, and long-term milestones for clinical translation, cost-effectiveness, and intellectual property. The key takeaway is that precision microbiome medicine in CVD will require standardized assays, prospective validation, robust regulatory pathways, and equitable commercialization. By linking mechanistic insights with translational requirements, this review provides a framework for developing microbiome-targeted diagnostics and therapeutics in CVD.