Abstract / Summary
Purpose: Emerging evidence links gut microbiota dysbiosis and its metabolites to atherosclerosis. This systematic review aims to synthesize prospective evidence on the association of gut microbiota and its metabolites with prognosis in coronary heart disease (CHD) patients.
Methods: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted from inception to January 21, 2026. Prospective cohort studies, nested case-control studies, or prospective case-control studies reporting associations between gut microbiota features or metabolite levels and major adverse cardiovascular and cerebrovascular events (MACCE, including all-cause death, cardiovascular death, myocardial infarction, stroke, unstable angina, heart failure, and all-cause unplanned hospitalization/emergency department visits) in CHD patients were included.
Results: Eighteen studies were included. Higher Lactobacillus abundance was associated with favorable prognosis, whereas a 10-species microbial risk score (MRS) predicted increased MACCE risk. For microbial metabolites, elevated trimethylamine N-oxide (TMAO) showed a consistent concentration-response association with increased MACCE risk. Phenylacetylglutamine (PAGln) and imidazole propionate (ImP) independently predicted poor outcomes in STEMI patients. Indole-3-propionic acid (IPA) was associated with reduced mortality, whereas deoxycholic acid (DCA) was associated with increased risk, while indoxyl sulfate (IS), acylcarnitines, and choline predicted worse outcomes. Mechanistically, these metabolites modulate inflammation, lipid metabolism, endothelial function, and platelet activation.
Conclusions: Gut microbial features, particularly Lactobacillus abundance, are associated with favorable prognosis, whereas specific microbial risk patterns predict increased risk. Metabolites TMAO, PAGln, and ImP are linked to poor outcomes, while IPA may confer protection and DCA is associated with increased risk. These findings not only provide new insights into the pathogenesis of coronary heart disease but also identify potential therapeutic targets for microbiota-based interventions.