| RRC ID |
88718
|
| 著者 |
Zha X, Liu X, Wei M, Huang H, Cao J, Liu S, Bian X, Zhang Y, Xiao F, Xie Y, Wang W, Zhang C.
|
| タイトル |
Microbiota-derived lysophosphatidylcholine alleviates Alzheimer's disease pathology via suppressing ferroptosis.
|
| ジャーナル |
Cell Metab
|
| 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.
|
| 巻・号 |
37(1)
|
| ページ |
169-186.e9
|
| 公開日 |
2025-1-7
|
| DOI |
10.1016/j.cmet.2024.10.006
|
| PII |
S1550-4131(24)00402-9
|
| PMID |
39510074
|
| MeSH |
Alzheimer Disease* / drug therapy
Alzheimer Disease* / metabolism
Alzheimer Disease* / microbiology
Alzheimer Disease* / pathology
Amyloid beta-Peptides / metabolism
Animals
Disease Models, Animal
Female
Ferroptosis* / drug effects
Gastrointestinal Microbiome* / drug effects
Humans
Lysophosphatidylcholines* / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
|
| リソース情報 |
| 一般微生物 |
JCM5826
JCM13471
JCM5827 |
