Manfredi John N, Gupta Sonu Kumar, Vyavahare Sagar, Deak Ferenc, Lu Xinyun, Buddha Lasya, Wankhade Umesh, Lohakare Jayant, Isales Carlos, Fulzele Sadanand
Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Deptment of Neuroscience & Regenerative Medicine, Augusta, GA 30912, USA.
Physiol Behav. 2025 Mar 1;290:114778. doi: 10.1016/j.physbeh.2024.114778. Epub 2024 Dec 11.
Alzheimer's Disease (AD) is a debilitating neurocognitive disorder with an unclear underlying mechanism. Recent studies have implicated gut microbiota dysbiosis with the onset and progression of AD. The connection between gut microbiota and AD can significantly affect the prevention and treatment of AD patients. This systematic review summarizes primary outcomes of human and mouse AD models concerning gut microbiota alterations. A systematic literature search in February through March 2023 was conducted on PubMed, Embase, and Web of Science. We identified 711 as potential manuscripts of which 672 were excluded because of irrelevance to the identified search criteria. Primary outcomes include microbiota compositions of control and AD models in humans and mice. In total, 39 studies were included (19 mouse and 20 human studies), published between 2017 and 2023. We included studies involving well-established mice models of AD (5xFAD, 3xTg-AD, APP/PS1, Tg2576, and APPPS2) which harbor mutations and genes that drive the formation of Aß plaques. All human studies were included on those with AD or mild cognitive impairment. Among alterations in gut microbiota, most studies found a decreased abundance of the phyla Firmicutes and Bifidobacteria, a genus of the phylum Actinomycetota. An increased abundance of the phyla Bacteroidetes and Proteobacteria were identified in animal and human studies. Studies indicated that gut microbiota alter the pathogenesis of AD through its impact on neuroinflammation and permeability of the gastrointestinal tract. The ensuing increase in blood-brain barrier permeability may accelerate Aβ penetrance and formation of neuritic plaques that align with the amyloid hypothesis of AD pathogenesis. Further studies should assess the relationship between gut microbiota and AD progression and therapy preserving beneficial gut microbiota.
阿尔茨海默病（AD）是一种使人衰弱的神经认知障碍，其潜在机制尚不清楚。最近的研究表明肠道微生物群失调与AD的发病和进展有关。肠道微生物群与AD之间的联系会显著影响AD患者的预防和治疗。本系统综述总结了人类和小鼠AD模型中肠道微生物群改变的主要结果。2023年2月至3月在PubMed、Embase和Web of Science上进行了系统的文献检索。我们确定了711篇潜在手稿，其中672篇因与确定的搜索标准无关而被排除。主要结果包括人类和小鼠对照及AD模型的微生物群组成。总共纳入了39项研究（19项小鼠研究和20项人类研究），发表于2017年至2023年之间。我们纳入了涉及成熟AD小鼠模型（5xFAD、3xTg-AD、APP/PS1、Tg2576和APPPS2）的研究，这些模型携带驱动Aβ斑块形成的突变和基因。所有人类研究均纳入了患有AD或轻度认知障碍的人群。在肠道微生物群的改变中，大多数研究发现厚壁菌门和放线菌门的双歧杆菌属丰度降低。在动物和人类研究中，拟杆菌门和变形菌门的丰度增加。研究表明，肠道微生物群通过影响神经炎症和胃肠道通透性来改变AD的发病机制。随之而来的血脑屏障通透性增加可能会加速Aβ的穿透和神经炎性斑块的形成，这与AD发病机制的淀粉样蛋白假说一致。进一步的研究应评估肠道微生物群与AD进展及保留有益肠道微生物群的治疗之间的关系。
