The gut-heart axis in coronary artery disease: a scoping and narrative review of sex-based microbial and metabolic disparities.

Background The gut microbiota significantly influences cardiovascular health by regulating host metabolism and generating bioactive compounds like trimethylamine-N-oxide (TMAO) and indoxyl sulfate (IS), both linked to coronary artery disease (CAD). Emerging research indicates sex-based differences in microbial composition and metabolite production, yet their impact on CAD pathophysiology remains unclear. This scoping review summarizes current findings on sex-specific microbial and metabolic differences in individuals with CAD.Methods A systematic search of PubMed and EMBASE was conducted through March 2025 for peer-reviewed studies comparing gut microbiota or metabolite profiles between male and female patients with CAD. Eligible studies used 16S rRNA sequencing, shotgun metagenomics, or metabolite profiling to analyze microbial communities and atherosclerosis-associated metabolites. Mechanistic links from genetics, epigenetics, and hormone-microbiota interactions were integrated to provide a more comprehensive understanding of how gut microbiota may contribute to sex differences in CAD.Results Eleven studies met the inclusion criteria for this review. Men with CAD exhibited increased relative abundances of taxa such as Prevotella, Clostridia_UCG_014, UCG_010, and other pro-inflammatory genera, whereas women microbiota was comparatively enriched in Barnesiella, Bifidobacteriales, and other potentially beneficial taxa. Parallel differences emerged in microbial metabolite profiles: men demonstrated elevated plasma levels of TMAO and IS, both associated with heightened cardiovascular risk and disease burden. Conversely, women with CAD had higher circulating levels of secondary bile acids and lower TMAO concentrations.Conclusion Preliminary studies suggest sex-related differences in gut microbiota composition and metabolite profiles in CAD patients. Integrating mechanistic links from microbial metabolism, genetics, epigenetics, and hormones supports a potential role of the microbiota in sex-dependent disease pathways. Current evidence is limited and mostly observational; well-designed studies are needed to clarify mechanisms, clinical relevance of sex-specific microbiome signatures and specifically assess whether these sex-specific microbial and metabolic differences influence CAD progression and outcomes.Men and women develop heart disease differently, and one possible explanation may lie in the gut microbiome—the community of bacteria living in our digestive system. These bacteria help digest food, regulate metabolism, and influence inflammation, all of which can affect the health of the heart’s arteries. Research on how the gut microbiome differs between men and women with coronary artery disease is still very limited, but early evidence suggests that men and women may have different gut bacterial communities. Men tend to have more bacteria linked to inflammation, while women often have bacteria that may support a healthier gut and immune system. These differences could influence how the body responds to inflammation, processes fats, and maintains healthy blood vessels over time. Although this is an emerging field and we are only beginning to understand these patterns, the findings suggest that the gut microbiome may play a role in why heart disease develops differently in men and women. More research is needed to confirm these observations and to explore whether understanding gut bacteria could lead to new, sex-specific approaches to prevent or treat heart disease in the future.