Summary
This narrative review synthesises evidence on how gut microbiota-derived tryptophan metabolites influence cardiovascular disease through three main metabolic pathways (indole, kynurenine, and serotonin), acting via gut barrier integrity, immune regulation and neuroendocrine signalling. The authors identify indoxyl sulfate, indole-3-propionic acid and indole-3-acetic acid as candidate biomarkers, and discuss precision intervention strategies spanning diet, probiotics, postbiotics, and traditional Chinese medicine. However, the authors acknowledge that current evidence is largely animal-derived or from small clinical cohorts, with critical gaps in standardised detection methods, causal inference, and clinical translation.
Regional applicability
The review addresses mechanistic pathways and candidate biomarkers that are likely relevant across populations, including the United Kingdom. However, applicability of specific precision interventions (particularly traditional Chinese medicine formulations and host-genetics-guided strategies) will require validation in UK-ancestry cohorts and consideration of existing dietary guidelines and regulatory pathways for probiotics and postbiotics.
Key measures
Concentrations and metabolic flux of indole derivatives, indoxyl sulfate (IS), indole-3-propionic acid (IPA), indole-3-acetic acid (IAA), kynurenine pathway metabolites, and serotonin; mechanisms via gut barrier function, Th17/Treg immune regulation, aryl hydrocarbon receptor (AhR) activation, and neuroendocrine blood pressure control
Outcomes reported
The review synthesises research on gut microbiota-derived tryptophan metabolites (indole derivatives, kynurenine, serotonin) and their roles in atherosclerosis, hypertension, heart failure and other cardiovascular diseases. It evaluates these metabolites as biomarkers and explores precision interventions including diet, probiotics, postbiotics, traditional Chinese medicine, and host-genetics-guided approaches.
Supporting research
Primary review explicitly considers dietary regimens, probiotic/postbiotic supplementation and tryptophan metabolism alongside other cardiovascular interventions.
Limits: Mixed mechanistic/clinical review, predominantly animal and small-cohort evidence; dietary preparations and their study designs need separation from medicinal compounds. No clinical dietary efficacy is certified.
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