EXPLORING THE GUT-BRAIN AXIS: THE ROLE OF THE MICROBIOME IN MODULATING BRAIN FUNCTION AND ITS IMPLICATIONS IN NEURODEGENERATIVE DISORDERS LIKE PARKINSON'S AND ALZHEIMER'S AND PHARMACOTHERAPY TREATMENT STRATEGIES

The gut-brain axis (GBA) represents a dynamic bidirectional communication network linking the gastrointestinal tract and the central nervous system, with the gut microbiome playing a pivotal role in modulating brain function and behavior. This review explores the mechanisms by which microbial communities influence neuroinflammation, synaptic plasticity, and neurodegeneration through neural, endocrine, and immune pathways, including the production of metabolites such as short-chain fatty acids (SCFAs), neurotransmitters, and pro-inflammatory cytokines. Dysbiosis, characterized by shifts in microbial diversity and function, is increasingly implicated in the pathogenesis of neurodegenerative disorders, particularly Alzheimer’s disease (AD) and Parkinson’s disease (PD). In AD, gut-derived metabolites like trimethylamine N-oxide (TMAO) and amyloidogenic proteins exacerbate neuroinflammation and amyloid-beta aggregation, while in PD, α-synuclein misfolding in the enteric nervous system precedes motor symptoms, propagating pathology via the vagus nerve. Emerging evidence underscores the microbiome’s role in disrupting blood-brain barrier integrity and promoting neurotoxic immune responses. Pharmacotherapeutic strategies targeting the GBA, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and small-molecule inhibitors, demonstrate potential in restoring microbial equilibrium and mitigating neurodegeneration. Clinical trials highlight the efficacy of Lactobacillus and Bifidobacterium strains in reducing cognitive decline, while FMT shows promise in alleviating motor symptoms in PD. Challenges such as microbiome heterogeneity, sex-specific responses, and translational gaps between preclinical models and human trials are critically evaluated. By integrating advances in multi-omics, artificial intelligence, and CRISPR-based microbial engineering, this review advocates for personalized approaches to harness the GBA’s therapeutic potential. Ultimately, targeting the gut microbiome offers a transformative paradigm for preventing and treating neurodegenerative diseases, shifting focus from symptomatic management to early intervention and disease modification.