Nutritional Intervention Strategies for Alzheimer's Disease from the Perspective of the Gut-Brain Axis

Abstract

As a progressive neurodegenerative disorder, Alzheimer's disease (AD) currently lacks curative treatments. Recent studies have demonstrated that gut dysbiosis modulates neuroimmune and metabolic pathways via the gut–brain axis and plays a pivotal role in AD pathological progression, which opens up new avenues for nutritional intervention. This paper systematically reviews multiple nutritional intervention strategies based on gut microecology regulation, including probiotics, prebiotics, polyphenolic antioxidants, omega‑3 fatty acids, and fecal microbiota transplantation (FMT). Such interventions exert certain protective effects by modulating gut microbiota composition, alleviating neuroinflammation, preserving blood‑brain barrier integrity, and slowing cognitive decline. Although existing clinical investigations have yielded several positive outcomes, the field is still confronted with prominent limitations such as high heterogeneity of intervention regimens, short follow‑up durations, small sample sizes, and inconsistent biomarkers and detection criteria. These drawbacks result in low levels of evidence, making it difficult to directly guide clinical practice. Furthermore, factors including poor patient adherence and interference from comorbidities and concomitant medications hinder the stable evaluation of intervention efficacy. Future research should rely on long‑term, multicenter, large‑sample randomized controlled trials (RCTs), combined with integrated multi‑omics analysis and individualized stratification strategies, to identify the most effective intervention combinations and their applicable populations. This review elaborates on mechanisms underlying the gut-brain axis, major nutritional intervention strategies, available clinical evidence, and prevailing challenges, aiming to provide references for subsequent research and translational applications in this field.