The gut–brain axis in neurodegeneration and neural repair: microbiome-driven modulation of CNS inflammation, neurogenesis, and recovery

Oluwaseye Emmanuel Olayemi, Olusoji Oyesola, Babatunde Okebule, Zainob Sobowale, Elizabeth Anthony

Abstract


Background: The gut–brain axis represents a dynamic, bidirectional communication network linking the gastrointestinal microbiota with central nervous system (CNS) function. Emerging research implicates gut dysbiosis in the progression of neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), as well as in the regulation of neuroinflammatory tone and adult neurogenesis. Understanding the microbial regulation of CNS integrity offers a novel vantage point for both neuropathology and recovery.

Methodology: This review synthesizes findings from recent preclinical and clinical studies that explore the mechanistic underpinnings of the gut–brain axis in neurodegeneration and neural repair. Emphasis is placed on germ-free models, microbiome sequencing in human cohorts, and interventional trials involving probiotics, dietary strategies, and fecal microbiota transplantation (FMT).

Results: Microbiota-derived metabolites such as short-chain fatty acids (SCFAs) and tryptophan catabolites influence neuroimmune responses, blood–brain barrier (BBB) integrity, and neurogenesis in the hippocampus and subventricular zone. Dysbiosis is associated with heightened microglial activation, impaired Aβ clearance, and α-synuclein aggregation. Conversely, modulation of the microbiota through probiotics or dietary interventions can attenuate neuroinflammation and improve cognitive and motor outcomes in both animal models and early-stage clinical trials.

Conclusion: The gut–brain axis is a critical modulator of CNS health, with disruptions contributing to neurodegeneration but also offering a therapeutic window for repair. Future work should address causality, interindividual variability, and ethical considerations of microbiome manipulation to enable precision interventions targeting brain resilience and regeneration.

 

Received: 20 July 2025

Accepted: 07 September 2025

Published: 16 September 2025


Keywords


Gut–brain axis, microbiota, neurogenesis, neurodegeneration, short-chain fatty acids.

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References


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DOI: https://dx.doi.org/10.21622/AMPDR.2025.05.2.1469

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Copyright (c) 2025 Oluwaseye Emmanuel Olayemi, Olusoji Adebusoye Oyesola, Babatunde Olufemi Okebule, Zainob Oluwaferanmi Sobowale, Elizabeth Chinenye Anthony

Advances in Medical, Pharmaceutical and Dental Research

E-ISSN: 2812-4898

P-ISSN: 2812-488X

 

Published by:

Academy Publishing Center (APC)

Arab Academy for Science, Technology and Maritime Transport (AASTMT)

Alexandria, Egypt

ampdr@aast.edu