首都医科大学张晨等研究人员合作发现，肠道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。该研究于2024年11月6日发表于国际一流学术期刊《细胞—代谢》。

研究人员表示，阿尔茨海默病（AD）是一种广泛的神经退行性疾病，迫切需要新的预防和治疗方法。

研究人员阐明了一个肠道-微生物群-大脑轴，这为实现这一目标提供了可操作的视角。

通过使用5xFAD小鼠模型，研究人员发现增加的梭状芽胞杆菌（Clostridium）丰度和减少的拟杆菌（Bacteroides）丰度是与β-淀粉样蛋白（Aβ）负担相关的关键特征。

用拟杆菌（Bacteroides ovatus）或其相关代谢物溶血磷脂酰胆碱（LPC）治疗，显著减少了Aβ负担并改善了认知障碍。

在机制上，LPC通过孤儿受体GPR119作用，抑制了ACSL4的表达，从而抑制了铁死亡并改善了AD的病理表现。从阿尔茨海默病患者的粪便和血清样本分析还显示，拟杆菌和LPC水平降低。

因此，该研究确定了一个由B.ovatus触发的途径来调节AD病理，并指出单一肠道微生物、代谢物或小分子化合物的使用可能会补充当前的AD预防和治疗方法。

附：英文原文

Title: Microbiota-derived lysophosphatidylcholine alleviates Alzheimer’s disease pathology via suppressing ferroptosis

Author: Xu Zha, Xicheng Liu, Mengping Wei, Huanwei Huang, Jiaqi Cao, Shuo Liu, Xiaomei Bian, Yuting Zhang, Fenyan Xiao, Yuping Xie, Wei Wang, Chen Zhang

Issue&Volume:

Abstract: 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.

DOI: 10.1016/j.cmet.2024.10.006

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00402-9