Alzheimer’s disease (AD) is a pervasive neurodegenerative disorder, and new approaches for its prevention and therapy are critically needed. Here, we elucidate a gut-microbiome-brain axis that offers actionable perspectives for achieving this objective. Using the 5xFAD mouse model, we identify increased Clostridium abundance and decreased Bacteroides abundance as key features associated with β-amyloid (Aβ) burden. Treatment with Bacteroides ovatus, or its associated metabolite lysophosphatidylcholine (LPC), significantly reduces Aβ load and ameliorates cognitive impairment. Mechanistically, LPC acts through the orphan receptor GPR119, inhibiting ACSL4 expression, thereby suppressing ferroptosis and ameliorating AD pathologies. Analysis of fecal and serum samples from individuals with AD also reveals diminished levels of Bacteroides and LPC. This study thus identifies a B.ovatus-triggered pathway regulating AD pathologies and indicates that the use of single gut microbiota, metabolite, or small molecule compound may complement current prevention and treatment approaches for AD.

中文翻译：

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微生物群衍生的溶血磷脂酰胆碱通过抑制铁死亡缓解阿尔茨海默病病理


阿尔茨海默病 （AD） 是一种普遍存在的神经退行性疾病，迫切需要新的预防和治疗方法。在这里，我们阐明了肠道-微生物组-大脑轴，为实现这一目标提供了可行的视角。使用 5xFAD 小鼠模型，我们确定梭菌丰度增加和拟杆菌属丰度降低是与 β-淀粉样蛋白 （Aβ） 负荷相关的关键特征。用卵形拟杆菌或其相关代谢物溶血磷脂酰胆碱 （LPC） 治疗，可显着降低 Aβ 负荷并改善认知障碍。从机制上讲，LPC 通过孤儿受体 GPR119 起作用，抑制 ACSL4 表达，从而抑制铁死亡并改善 AD 病理。对 AD 个体的粪便和血清样本的分析也显示拟杆菌门和 LPC 水平降低。因此，本研究确定了调节 AD 病理的 B.ovatus 触发的途径，并表明使用单一肠道微生物群、代谢物或小分子化合物可能补充当前 AD 的预防和治疗方法。