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Updated: Apr 14, 2026

A Gut-on-a-Chip Model to Study the Gut Microbiome-Nervous System Axis
Published on: July 28, 2023
Brain-gut-microbiota axis: a review on the bidirectional regulatory mechanisms between gut microbiota and brain and
Hui Shen1,2,3, Si Yun Wang2,4, Yan Yan Zhao2,4
1National-Local Joint Engineering Research Center for Drug Research and Development of Neurodegenerative Diseases, Dalian Medical University, Dalian, Liaoning, China.
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.
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