Brain-gut-microbiota axis: a review on the bidirectional regulatory mechanisms between gut microbiota and brain and their disease interactions

Objective To synthesize current evidence on the bidirectional regulatory mechanisms of the Brain-Gut-Microbiota Axis (BGMA), its perturbation by external factors, and its clinical implications for neurodegenerative, psychiatric, metabolic, and gastrointestinal disorders. Design Narrative review integrating preclinical and clinical evidence. Data sources PubMed/Medline, EMBASE, Cochrane Library searches (2000–2023) using keywords: “brain-gut-axis,” “microbiota,” “dysbiosis,” “neuroinflammation,” “SCFAs,” “neurodegeneration,” “psychobiotics.” Results Diet, stress, antibiotics, and environment significantly alter gut microbiota composition (e.g., reducing diversity, shifting Firmicutes/Bacteroidetes (F/B) ratio). Dysbiosis disrupts BGMA communication via: (1) Neural pathways (vagus nerve modulation); (2) Immune activation (cytokine release, neuroinflammation); (3) Microbial metabolites (SCFAs, tryptophan derivatives, TMAO). These disruptions are associated with Alzheimer’s disease (reduced Faecalibacterium , amyloid deposition), Parkinson’s (elevated TMAO, α -synuclein aggregation), and depression (altered serotonin synthesis), though causality remains to be established in human studies. Conclusion The BGMA is a critical mediator of systemic health. Dysbiosis contributes to disease pathogenesis through defined neural, immune, and metabolic pathways. Targeting the microbiota offers novel therapeutic strategies. Future research must prioritize translational studies validating microbial biomarkers and interventions in human cohorts.