Targeting the gut–brain axis: novel strategies for disease intervention from mechanisms to clinical practice

Abstract

The gut–brain axis is a bidirectional communication network linking the gastrointestinal tract and the central nervous system (CNS), in which the gut microbiota and its metabolites have emerged as important modulators. Alterations in the gut microbiota have been reported in a range of neurological, psychiatric, and metabolic disorders, but their underlying mechanisms and causal relevance in humans are still unclear. This review examines the major neural, endocrine, immune, and metabolic pathways involved in microbiota–gut–brain communication and discusses how their disruption may affect neurotransmitter signaling, inflammation, barrier function, and host metabolism. We also review current intervention strategies, including microbiota modulation, dietary and metabolic approaches, neural and immunomodulatory interventions, and behavioral and traditional Chinese medicine (TCM) approaches. Particular attention is given to the strength of the available evidence, its clinical relevance, and the limitations and safety considerations that need to be addressed before gut–brain-axis-based strategies can be more widely applied.