Gut-Brain Axis Dysfunction in Alzheimer's and Parkinson's Diseases: The Role of Dysbiosis, Inflammation, and Therapeutic Targets — A Literature Review

Abstract

Introduction: Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative disorders, causing progressive cognitive and motor decline. High rates of new diagnoses, coupled with increasing evidence linking gastrointestinal (GI) dysfunction to neurodegeneration, highlight the significance of understanding the gut-brain axis (GBA). Changes in gut microbiota composition are associated with amyloid-beta accumulation in AD and α-synuclein aggregation in PD, suggesting that gut dysbiosis and inflammation may worsen disease pathology.

Methods: A systematic literature review was conducted using peer-reviewed primary research articles published between 2014 and 2025. Articles were selected based on their relevance to GI inflammation, gut microbiota dysbiosis, and neurodegenerative diseases. Studies involving human participants and relevant animal models were prioritized. Databases searched included PubMed, Google Scholar, ScienceDirect, JSTOR, and SpringerLink.

Results: Gut dysbiosis was consistently associated with increased intestinal permeability, systemic inflammation, and neuroinflammatory responses in AD and PD. Specific microbial imbalances correlated with accelerated disease progression and cognitive decline. Animal studies demonstrated that fecal microbiota transplantation from diseased individuals worsened motor and mental symptoms, while interventions targeting gut health, such as probiotics and dietary modifications, reduced neuroinflammation and improved outcomes.

Discussion: Findings support the GBA’s critical role in mediating neurodegeneration through immune activation and inflammatory pathways. Dysbiosis-induced changes in microbial metabolite production, including short-chain fatty acids (SCFAs) and tryptophan derivatives, further contribute to neuroinflammatory processes. Despite promising preclinical results, challenges remain in translating gut-targeted therapies to clinical use due to variability in individual microbiomes and limited longitudinal human data.

Conclusion: This review emphasizes the gut microbiota as a modifiable factor in the pathogenesis of AD and PD. Targeting GI inflammation and restoring microbial balance may offer novel therapeutic strategies for slowing disease progression. Future research should focus on validating gut-derived biomarkers, personalizing microbiome-based treatments, and conducting longitudinal clinical trials to optimize gut-brain interventions in neurodegenerative diseases.