Abstract
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.