Microbial Aromatic Amino Acid Metabolism in Cardiometabolic Disease

The gut microbiota generates a diverse array of metabolites that influence host physiology. Among these, products of microbial metabolism of the aromatic amino acids tryptophan, phenylalanine, tyrosine, and histidine have emerged as important components of host-microbiome interactions relevant to cardiometabolic disease. This Review summarizes the microbial pathways, enzymes, and metabolic networks involved in aromatic amino acid metabolism and examines how dietary substrate availability, microbial community composition, microbial enzymatic capacity, host metabolism, and environmental factors influence metabolite production and biological activity. Microbiota-derived metabolites and host-microbial co-metabolites are associated with inflammation, vascular function, thrombosis, metabolic homeostasis, and host signaling pathways. Their biological effects are context-dependent and influenced by microbial pathway activity, host metabolic processing, tissue compartment, disease stage, and substrate availability. We further distinguish evidence derived from human observational studies, experimental metabolite administration, and demonstrated molecular mechanisms. Finally, we discuss strategies to modulate aromatic amino acid metabolism, including dietary interventions, functional foods, probiotics, fecal microbiota transplantation, microbial enzyme inhibitors, and metabolite sequestration approaches. Current evidence supports a framework linking dietary substrates, microbial enzyme activity, host responses, and cardiometabolic phenotypes, while highlighting important opportunities and challenges for developing precision microbiome-based therapeutics.