Microbiota–Gut–Brain Axis in Alzheimer’s Disease: Linking Oxidative Stress, Mitochondrial Dysfunction and Amyloid Pathology—A Systematic Review

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, and mitochondrial dysfunction. Emerging evidence indicates that the gut microbiota plays a critical role in modulating neuroinflammatory, and metabolic pathways involved in AD pathogenesis through the microbiota-gut-brain axis. Objective: This systematic review aims to comprehensively evaluate the role of the microbiota-gut-brain axis in Alzheimer’s disease, with a particular focus on its mechanistic links to oxidative stress, mitochondrial dysfunction, and amyloid pathology, as well as its therapeutic potential. Methodology: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases, focusing on studies evaluating gut microbiota composition, metabolomic changes, oxidative stress markers, mitochondrial activity, and therapeutic interventions in AD models and patients. Results: Altered gut microbial composition in AD is associated with increased pro-inflammatory taxa (Escherichia-Shigella, Bacteroides) and depletion of short-chain fatty acid (SCFA) producing bacteria (Faecalibacterium, Roseburia). Dysbiosis contributes to systemic inflammation, disrupted intestinal permeability, and microglial activation, leading to oxidative damage and mitochondrial impairment in neurons. Preclinical and clinical studies indicate that probiotics, prebiotics, and fecal microbiota transplantation can restore redox balance, reduce neuroinflammation, and improve cognitive outcomes. Multi-omics and AI-based models are emerging as tools for identifying microbiome-derived biomarkers for early AD detection. Conclusion: The gut microbiota-mitochondria-oxidative stress axis represents a promising therapeutic target in Alzheimer’s disease. Future research should focus on longitudinal human studies, standardized microbial profiling, and personalized microbiome-based interventions to translate these mechanistic insights into clinical benefit.