Therapeutic Modulation of the Gut Microbiome in Coronary Artery Disease: Current Evidence and Future Directions

The gut microbiome is increasingly recognized as a modifiable contributor to coronary artery disease (CAD). This narrative review integrates mechanistic and clinical evidence regarding short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and bile acids, and appraises therapeutic modulation via diet; probiotics, prebiotics, and synbiotics; fecal microbiota transplantation (FMT); and drug-microbiome interactions. SCFAs generally confer anti-inflammatory and lipid-regulatory effects, whereas bile acid signaling exhibits context-dependent metabolic actions. Findings regarding TMAO are inconsistent; in several cohorts, associations with cardiovascular risk become null or attenuated after adjustment for renal function (estimated glomerular filtration rate [eGFR]) and dietary patterns. Most interventional studies are small, use surrogate endpoints, and vary in strains and dosing, limiting certainty. Microbiome profiles differ across geographic regions, racial and ethnic groups, and dietary patterns, underscoring the need for stratified approaches. Routine FMT in CAD remains constrained by safety, feasibility, and ethical and logistical considerations. Overall, the microbiome represents a promising yet unproven therapeutic target in CAD. Future trials should standardize interventions, rigorously control for confounders, evaluate drug-microbiome interactions, and be adequately powered to detect clinical events to enable precision medicine.