2. Academic Validation
  3. Microbiota-derived lysophosphatidylcholine alleviates Alzheimer's disease pathology via suppressing ferroptosis

Microbiota-derived lysophosphatidylcholine alleviates Alzheimer's disease pathology via suppressing ferroptosis

  • Cell Metab. 2024 Nov 1:S1550-4131(24)00402-9. doi: 10.1016/j.cmet.2024.10.006.
Xu Zha 1,  Xicheng Liu 2,  Mengping Wei 3,  Huanwei Huang 3,  Jiaqi Cao 3,  Shuo Liu 3,  Xiaomei Bian 3,  Yuting Zhang 3,  Fenyan Xiao 3,  Yuping Xie 4,  Wei Wang 5,  Chen Zhang 6
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair & Beijing Key Laboratory for Tumor Invasion and Metastasis, Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China; State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China.
  • 2 School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair & Beijing Key Laboratory for Tumor Invasion and Metastasis, Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China; State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China. Electronic address: liuxicheng@ccmu.edu.cn.
  • 3 School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair & Beijing Key Laboratory for Tumor Invasion and Metastasis, Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China.
  • 4 National Center for Protein Sciences Beijing, State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, China.
  • 5 School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair & Beijing Key Laboratory for Tumor Invasion and Metastasis, Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China. Electronic address: wangwei@ccmu.edu.cn.
  • 6 School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair & Beijing Key Laboratory for Tumor Invasion and Metastasis, Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China; State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China; Chinese Institute for Brain Research, Beijing, China. Electronic address: czhang@ccmu.edu.cn.
PMID: 39510074 DOI: 10.1016/j.cmet.2024.10.006
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.

Keywords

Alzheimer’s disease; Bacteroides ovatus; GPR119; ferroptosis; gut microbiota; lysophosphatidylcholine; β-amyloid.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z