Research Progress on the Gut–Brain Axis in the Pathogenesis and Progression of Alzheimer’s Disease

Abstract

Memory impairment and broader cognitive decline emerge gradually in Alzheimer’s disease (AD), although amyloid-β deposition, tau abnormalities, and neuroinflammatory changes often develop well before the clinical picture is fully established. Drug therapy can lessen selected symptoms, but it does not prevent continuing neuronal loss, and its long-term value is further limited by adverse effects and inadequate delivery across the blood–brain barrier. These shortcomings have increased interest in the microbiota–gut–brain axis (MGBA) as a framework for studying how intestinal biology may influence the brain. In this framework, microbial products and host responses are transmitted through vagal, endocrine, immune, and metabolic routes, while central nervous system activity can in turn alter intestinal conditions. This review evaluates those reciprocal pathways and discusses the roles of the hypothalamic–pituitary–adrenal axis, inflammatory signaling, short-chain fatty acids, tryptophan-derived metabolites, and trimethylamine N-oxide. It then examines microbial diversity and composition in AD and considers evidence for probiotics, fecal microbiota transplantation, and lifestyle-based intervention. Reports of dysbiosis before overt cognitive decline suggest that microbial change may participate in early disease development rather than simply accompany advanced pathology. That possibility remains unproven because most mechanistic evidence comes from animal models and much of the human literature is cross-sectional. Differences in cohort selection, sampling, and control of confounding variables further weaken causal interpretation. Longitudinal cohorts, integrated multi-omics analysis, and clinically meaningful patient stratification will therefore be essential for determining whether the MGBA can be used in AD prevention or treatment.