Beyond the gut: decoding the gut–immune–brain axis in health and disease

Abstract Emerging research underscores the pivotal role of the gut–immune–brain axis, a dynamic bidirectional communication system involving intricate interactions between the gut microbiota, immune responses, and the central nervous system. Gut microbes and their metabolites have profound effects on immune and neurological homeostasis, influencing the development and function of multiple physiological systems. Disruption of the composition of the gut microbiota and barrier integrity has been implicated in various neurological and psychiatric disorders, including autism spectrum disorder, Alzheimer’s disease, Parkinson’s disease, depression, and anxiety. Most insights into these host–microbiota interactions come from preclinical models, revealing both the complexity and potential therapeutic opportunities of the gut–brain communication pathways. This review synthesizes the current understanding of these intricate interactions, exploring how microbiota-driven modulation of the gut and brain barriers, immune signaling, and neuronal pathways, such as those through the vagus nerve, contributes to health and disease. We further explore therapeutic implications, including personalized precision microbiota interventions, microbiome-derived biomarkers, and barrier-strengthening strategies. Advancing this field offers transformative potential for developing innovative, personalized therapies tailored to individual microbiomes and immune profiles, ultimately redefining clinical approaches to neurological and immune-mediated diseases.