Fecal Microbiota Transplantation in Alzheimer’s Disease: Mechanistic Insights Through the Microbiota–Gut–Brain Axis and Therapeutic Prospects

作者：Jiayu Ren, Qinwen Wang, Hang Hong, Chunlan Tang · 发表于：Microorganisms · 年份：2025 · DOI：10.3390/microorganisms13081956 · 被引用次数：15 · 研究领域：Clostridium difficile and Clostridium perfringens research、Gut microbiota and health、Gastrointestinal motility and disorders

Alzheimer's disease (AD), a prevalent neurodegenerative disorder in the aging population, remains without definitive therapeutic solutions. Emerging insights into the gut microbiota (GM) and its bidirectional communication with the central nervous system(CNS) through the microbiota-gut-brain axis (MGBA) have unveiled potential correlative mechanisms that may contribute to AD pathogenesis, though causal evidence remains limited. Dysregulation of GM composition (dysbiosis) exacerbates AD progression via neuroinflammation, amyloid-β (Aβ) deposition, and tau hyperphosphorylation (p-tau), while restoring microbial homeostasis presents a promising therapeutic strategy. Fecal microbiota transplantation (FMT), a technique to reconstitute gut ecology by transferring processed fecal matter from healthy donors, has demonstrated efficacy in ameliorating cognitive deficits and neuropathology in AD animal models. Preclinical studies reveal that FMT reduces Aβ plaques, normalizes tau phosphorylation, suppresses inflammasome activation, and restores microglial homeostasis through modulation of microbial metabolites and immune pathways. Although clinical evidence remains limited to case reports and small-scale trials showing potential therapeutic effect, safety concerns regarding long-term effects and protocol standardization necessitate further investigation. This review synthesizes current knowledge on GM-AD interactions, evaluates FMT's mechanistic potential, and discusses challenges in tr...