A Comprehensive Review of the Gut–Microbiota–Brain Axis in Alzheimer’s Disease: From Pathophysiology to Potential Therapies

The gut–microbiota–brain axis (GMBA), an intricate network connecting the gastrointestinal (GI) tract and the brain, plays a pivotal role in maintaining overall health and influencing disease processes. The human gut microbiota, comprising over 3000 bacterial species, regulates immune responses, hormonal signals, and metabolite production, maintaining homeostasis under normal conditions. Dysbiosis, or microbial imbalance, has been linked to various central nervous system (CNS) disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and autism spectrum disorder (ASD). Given the growing interest in this topic and the limited effectiveness of current therapeutic strategies for managing patients with AD, the purpose of the current narrative review is to analyze the pathophysiological role of the GMBA in the pathogenesis of AD and assess potential therapeutic strategies targeting the GMBA, particularly the microbiome and its metabolites. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science to identify clinical studies, experimental research, and review articles examining the GMBA in health and AD, as well as related therapeutic strategies. The search terms included “Alzheimer’s disease”, “neuroinflammation”, “amyloid-beta”, “tau”, “gut–brain axis”, “microbiome”, “short-chain fatty acids”, “probiotics”, “prebiotics”, and “fecal microbiota transplantation”. In AD, altered gut microbiota composition is associated with neuroinflammation, neurodegeneration, and exacerbation of disease progression. Probiotics have shown potential in enhancing cognitive function and reducing neuroinflammation by modulating microbiota composition and influencing brain-derived neurotrophic factor (BDNF) levels. Prebiotics, through their impact on gut microbiota and metabolite production, also offer therapeutic promise by improving cognitive function and mitigating neuroinflammation. With its historical and modern applications, fecal microbiota transplantation (FMT) may represent a potential strategy for addressing dysbiosis and its neurological implications. This manuscript focuses on GMBA and its effects on neuroinflammation, neurodegeneration, and CNS health while emphasizing the need for further research into microbiome-based therapies and the gut–brain relationship in patients with AD.