Regulation of histidine metabolism by Lactobacillus Reuteri mediates the pathogenesis and treatment of ischemic stroke  

作　　者：Kangrui Hu Zhihao Zhou Haofeng Li Jijun Xiao Yun Shen Ke Ding Tingting Zhang Guangji Wang Haiping Hao Yan Liang 

机构地区：[1]Key Lab of Drug Metabolism&Pharmacokinetics,State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China [2]Ministry of Education Key Laboratory of Protein Science,Beijing Advanced Innovation Center for Structural Biology,Beijing Frontier Research Center for Biological Structure,Tsinghua-Peking Center for Life Sciences,School of Life Sciences,Tsinghua University,Beijing 100084,China [3]School of Materials Science and Engineering,Hebei University of Science and Technology,Shijiazhuang 050023,China

出　　处：《Acta Pharmaceutica Sinica B》2025年第1期239-255,共17页药学学报(英文版)

基　　金：supported by the National Natural Science Foundation of China(82274194);the Jiangsu Natural Science Funds(BK20211224,China);the Natural Science Foundation of Hebei Province(H_(2)020208025,H_(2)021208006,H_(2)021302001,C2021418001,China);the CAMS Innovation Fund for Medical Sciences(2021-I2M-5-011,China).

摘　　要：Increasing evidence has underscored the significance of post-stroke alterations along gutebrain axis,while its role in pathogenesis and treatment of ischemic stroke(IS)remains largely unexplored.This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins(PNS)on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gutebrain axis.Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent.Ischemia/reperfusion(I/R)modeling significantly downregulated Lactobacilli in rats,and PNS markedly recovered Lactobacilli,particularly Lactobacillus reuteri(L.Reu).Metabolomics showed a significant reduction in serum histidine(HIS)in clinical obsolete IS patients and rehabilitation period I/R rats.Meanwhile,the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum,gut microbiota,and brain.Moreover,exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine.Notably,vagus nerve severance in I/R rats was performed to investigate HIS’s neuroprotective mechanism.The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion,thereby increasing intracerebral HIS through peripheral pathway.Consequently,our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.

关 键 词：Ischemic stroke Inflammation Gut-brain axis Panaxnotoginseng saponins Lactobacillus reuteri Metabolomics HISTIDINE HISTAMINE 

分 类 号：R28[医药卫生—中药学]