Lista Simone, Munafò Antonio, Caraci Filippo, Imbimbo Camillo, Emanuele Enzo, Minoretti Piercarlo, Pinto-Fraga José, Merino-País María, Crespo-Escobar Paula, López-Ortiz Susana, Monteleone Giovanni, Imbimbo Bruno P, Santos-Lozano Alejandro
i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence 50139, Italy.
Ageing Res Rev. 2025 Feb;104:102659. doi: 10.1016/j.arr.2025.102659. Epub 2025 Jan 10.
Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks. Additionally, we examine other pathophysiological mechanisms by which GM may influence AD risk, including the production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites. The role of the vagus nerve in gut-brain communication is also addressed. We highlight potential therapeutic implications of targeting GM in AD, focusing on antibiotics, probiotics, prebiotics, postbiotics, phytochemicals, and fecal microbiota transplantation. While preclinical studies showed promise, clinical evidence remains limited and inconsistent. We critically assess clinical trials, emphasizing challenges in translating GM-based therapies to AD patients. The reviewed evidence underscores the need for further research to elucidate precise molecular mechanisms linking GM to AD and determine whether GM dysbiosis is a contributing factor or consequence of AD pathology. Future studies should focus on large-scale clinical trials to validate GM-based interventions' efficacy and safety in AD.
越来越多的证据表明，肠道微生物群（GM）在阿尔茨海默病（AD）的发病机制和进展中起着关键作用。这篇叙述性综述探讨了GM、免疫系统和中枢神经系统在AD中的复杂相互作用。我们讨论了GM失调可能损害肠道屏障完整性的机制，使促炎分子和代谢产物进入体循环和大脑，这可能导致AD的特征。此外，我们研究了GM可能影响AD风险的其他病理生理机制，包括短链脂肪酸、次级胆汁酸和色氨酸代谢产物的产生。还讨论了迷走神经在肠脑通讯中的作用。我们强调了针对GM治疗AD的潜在意义，重点关注抗生素、益生菌、益生元、后生元、植物化学物质和粪便微生物群移植。虽然临床前研究显示出前景，但临床证据仍然有限且不一致。我们对临床试验进行了批判性评估，强调了将基于GM的疗法应用于AD患者所面临的挑战。所审查的证据强调需要进一步研究，以阐明将GM与AD联系起来的精确分子机制，并确定GM失调是AD病理的促成因素还是后果。未来的研究应侧重于大规模临床试验，以验证基于GM的干预措施在AD中的疗效和安全性。
