The Gut-Brain Axis in Alzheimer's Disease: Exploring Microbial Influences and Therapeutic Strategies

Microbiota residing in the human gastrointestinal tract play a critical role in maintaining homeostasis through immune regulation, metabolic activity, and signaling to the central nervous system. Recent studies have highlighted the influence of gut microbiota on neurodegenerative diseases, particularly Alzheimer's disease (AD), through the microbiota-gut-brain axis. This bidirectional communication system involves neural, hormonal, and immunological pathways, linking gut health directly with brain function. Disruption of the gut microbial balance-known as dysbiosis-has been associated with increased amyloid-beta (Aβ) deposition, tau hyperphosphorylation, oxidative stress, neuroinflammation, and impaired neurotransmission, all of which are key pathological features of AD. Microbial metabolites such as short-chain fatty acids, trimethylamine N-oxide, and gasotransmitters influence the permeability of the blood-brain barrier and modulate neuroimmune responses. Emerging evidence also indicates that gut microbiota may contribute to the early onset and progression of AD through systemic inflammation and metabolic dysfunction. Modulating the gut microbiome, therefore, presents a novel avenue for therapeutic intervention. This review aims to synthesize current findings on how gut microbiota alterations contribute to AD pathology. Furthermore, it explores therapeutic strategies-including diet, probiotics, prebiotics, polyphenols, and fecal microbiota transplantation-that hold potential in restoring microbial balance and mitigating cognitive decline in AD.