Virulence. 2026 Dec;17(1):2670787. doi: 10.1080/21505594.2026.2670787. Epub 2026 Jun 2.
ABSTRACT
Obesity, a global epidemic, drives coronary microvascular dysfunction (CMD), a precursor to cardiovascular disease, via gut microbiota dysbiosis. Clinical evidence shows a 47.7% reduction in coronary flow reserve among obese patients, highlighting obesity's pivotal role in CMD pathogenesis. This review elucidates molecular mechanisms linking obesity-induced dysbiosis to CMD, focusing on microbial metabolites: TMAO promotes lipid deposition and inflammation; reduced SCFAs impair endothelial function; bile acids modulate vascular tone via FXR/TGR5; LPS induces metabolic endotoxemia; BCAAs trigger insulin resistance; endogenous ethanol fosters oxidative stress; indole metabolites exert dual vascular effects; ImP and PAGln accelerate atherosclerosis and thrombosis; and H2S deficiency and elevated succinate exacerbate remodeling. The gut-heart axis amplifies CMD risk beyond traditional factors. Future multi-omics studies should identify biomarkers and develop targeted therapies, such as metabolite inhibitors and precision nutrition, to mitigate obesity-related CMD and improve outcomes. The Graphical Abstract is presented in Figure 1.[Figure: see text].
PMID:42228778 | DOI:10.1080/21505594.2026.2670787