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

Eleven studies met inclusion criteria for this scoping review of sex-specific gut microbiota and metabolite profiles in CAD patients.

• A systematic search of PubMed and EMBASE was conducted through March 2025.
• Eligible studies used 16S rRNA sequencing, shotgun metagenomics, or metabolite profiling to analyze microbial communities and atherosclerosis-associated metabolites.
• Studies were required to compare gut microbiota or metabolite profiles between male and female patients with CAD.
• Only peer-reviewed studies were included.

Men with CAD exhibited increased relative abundances of pro-inflammatory microbial taxa compared to women.

• Taxa enriched in men with CAD included Prevotella, Clostridia_UCG_014, UCG_010, and other pro-inflammatory genera.
• Women with CAD had microbiota comparatively enriched in Barnesiella, Bifidobacteriales, and other potentially beneficial taxa.
• These differences suggest sex-specific gut microbial community compositions in the context of CAD.

Men with CAD demonstrated elevated plasma levels of TMAO and indoxyl sulfate (IS) compared to women.

• Both TMAO and IS were described as associated with heightened cardiovascular risk and disease burden.
• Conversely, women with CAD had higher circulating levels of secondary bile acids.
• Women with CAD had lower TMAO concentrations relative to men.
• These parallel differences in metabolite profiles mirrored the sex-specific differences observed in microbial composition.

Mechanistic links from genetics, epigenetics, and hormone-microbiota interactions were integrated to explain how gut microbiota may contribute to sex differences in CAD.

• The review integrated mechanistic links from microbial metabolism, genetics, epigenetics, and hormones.
• These mechanisms were described as supporting 'a potential role of the microbiota in sex-dependent disease pathways.'
• Sex hormones are implicated in shaping gut microbial composition and metabolite production differentially in men and women.

Current evidence on sex-specific gut microbiome differences in CAD is limited and mostly observational.

• The authors describe the current evidence as 'limited and mostly observational.'
• Well-designed studies are needed to clarify mechanisms and the clinical relevance of sex-specific microbiome signatures.
• It remains unclear whether sex-specific microbial and metabolic differences influence CAD progression and outcomes.
• The authors call for studies that 'specifically assess whether these sex-specific microbial and metabolic differences influence CAD progression and outcomes.'

The gut microbiota influences cardiovascular health by regulating host metabolism and generating bioactive compounds linked to CAD.

• Key bioactive compounds discussed include trimethylamine-N-oxide (TMAO) and indoxyl sulfate (IS), both linked to coronary artery disease.
• The gut microbiota regulates host metabolism and generates these compounds through microbial metabolic activity.
• The review frames this relationship as the 'gut-heart axis' in the context of coronary artery disease.