Gut microbial metabolites: linking gut–immune–brain crosstalk to mental and neuropsychiatric health

This narrative review adopts the gut-immune-brain axis as the core framework. Literature published 2010-2025 was retrieved from PubMed, Web of Science and ScienceDirect; landmark pre-2010 studies from top journals were also included. Literature was analyzed across five dimensions: metabolite synthesis-transport, intestinal immune regulation, central mediation, disease-pathology links and clinical translation. We elucidate how short-chain fatty acids, tryptophan metabolites and bile acids act as immune messengers to modulate neural homeostasis. Under physiological conditions, they maintain barrier integrity and central immune balance; when dysregulated, they trigger immune disturbance, blood-brain barrier damage and neuroinflammation, promoting Alzheimer’s disease, Parkinson’s disease, major depressive disorder and chronic insomnia. Moving beyond conventional gut-brain-axis reviews focused merely on gut-brain communication, this work highlights immunity as the critical intermediate node and constructs the cascade “gut microbial metabolites-immune regulation-neural homeostasis-disease”. We further summarize biomarker prospects and intervention strategies including dietary fiber, pre-/probiotics and fecal microbiota transplantation. Notably, an ICH-M10-aligned five-stage biomarker validation framework and a gut-brain-immune tri-culture microfluidic model are proposed, offering new directions for mechanistic research and precision therapy for neurological disorders.