Gut microbiota-derived tryptophan metabolites in cardiovascular disease: mechanisms, biomarkers, and precision interventions

Abstract

The gut microbiota plays a significant role in cardiovascular disease (CVD), through its metabolic products. Tryptophan is a key signaling molecule in the microbiota–host network; its gut microbial metabolites, including indole derivatives, kynurenine and serotonin, have dual effects on cardiovascular homeostasis. This review summarizes research progress on gut microbiota-derived tryptophan metabolites in atherosclerosis, hypertension, heart failure and other CVDs, focusing on metabolic flux in three pathways, the indole, kynurenine (KYN) and 5-hydroxytryptamine (5-HT) pathways, and their mechanisms via gut barrier maintenance, immune regulation through Th17/Treg and aryl hydrocarbon receptor (AhR) axis, and neuroendocrine blood pressure control. It also evaluates clinical evidence for key metabolites, such as indoxyl sulfate (IS), indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA), as novel biomarkers, and explores precision interventions including dietary regimens, probiotic or postbiotic supplementation, traditional Chinese medicine ingredients, and host genetic background-guided strategies. Current evidence shows these metabolites exert both protective and pathogenic effects, highly dependent on disease context, microenvironment and host genetics. However, most data are from animal models and small cohort studies; remaining challenges include detection standardization, causality establishment and clinical translation. Future research should employ large prospective cohorts, multi-omics integration and mechanism-driven intervention trials to systematically elucidate the regulatory network and advance precision prevention and treatment.