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Diet, the Gut Microbiome, and Mental Health: Mechanistic Perspectives

Hetta HF, Hassan RAA, Alanazi FE, Alqifari SF, Albalwi MA, Albalawi AA, Bukhari SQ, Alatawi Z et al.

Molecular nutrition & food research, 2026

Abstract

The microbiota-gut-brain axis (MGBA) represents a dynamic, bidirectional communication network linking the gut microbiome with central nervous system function through neural, immune, metabolic, and endocrine pathways. Emerging clinical, observational, and preclinical evidence suggests that special and restrictive dietary patterns-including Mediterranean, ketogenic, vegan, gluten-free, low-FODMAP, sugar-restricted, dairy-free diets, and intermittent fasting (IF)-can substantially modulate the gut microbiota, potentially influencing mental health outcomes. In this review, we first outline the fundamental mechanisms underlying gut-brain communication, emphasizing the roles of microbial metabolites, vagal nerve signaling, immune modulation, and hypothalamic-pituitary-adrenal (HPA) axis interactions. We then examine how distinct dietary interventions may alter gut microbial composition and metabolic activity, with potential implications for neuroimmune regulation, neurotransmitter synthesis, gut barrier integrity, and stress resilience. Current limitations in the field-including population heterogeneity, interindividual microbiome variability, limited longitudinal and mechanistic human studies, and challenges in clinical translation-are critically discussed. Finally, we propose future research directions aimed at developing personalized dietary strategies for mental health support through microbiome-targeted approaches. Understanding how special diets reshape the MGBA may provide…

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