FLZ attenuates Parkinson's disease pathological damage by increasing glycoursodeoxycholic acid production via down-regulating Clostridium innocuum  

作　　者：Meiyu Shang Jingwen Ning Caixia Zang Jingwei Ma Yang Yang Yueqi Jiang Qiuzhu Chen Yirong Dong Jinrong Wang Fangfang Li Xiuqi Bao Dan Zhang 

机构地区：[1]State Key Laboratory of Bioactive Substrate and Function of Natural Medicine,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

出　　处：《Acta Pharmaceutica Sinica B》2025年第2期973-990,共18页药学学报(英文版)

基　　金：supported by The National Key Research and Development Program of China(grant No.2023YFC3502800);the CAMS Innovation Found for Medical Sciences(No.2022-I2M-2-001,China).

摘　　要：Increasing evidence shows that the early lesions of Parkinson's disease(PD)originate from gut,and correction of microbiota dysbiosis is a promising therapy for PD.FLZ is a neuroprotective agent on PD,which has been validated capable of alleviating microbiota dysbiosis in PD mice.However,the detailed mechanisms still need elucidated.Through metabolomics and 16S rRNA analysis,we identified glycoursodeoxycholic acid(GUDCA)was the most affected differential microbial metabolite by FLZ treatment,which was specially and negatively regulated by Clostridium innocuum,a differential microbiota with the strongest correlation to GUDCA production,through inhibiting bile salt hydrolase(BSH)enzyme.The protection of GUDCA on colon and brain were also clarified in PD models,showing that it could activate Nrf2 pathway,further validating that FLZ protected dopaminergic neurons through promoting GUDCA production.Our study uncovered that FLZ improved PD through microbiota-gut-brain axis,and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

关 键 词：Parkinson's disease FLZ Glycoursodeoxycholic acid Clostridium innocuum Gut-brain axis Microbiota dysbiosis Microbial metabolites NEUROINFLAMMATION 

分 类 号：R742.5[医药卫生—神经病学与精神病学]