Landscapes of gut microbiome and blood metabolomic signatures in relapsing remitting multiple sclerosis  

作　　者：Jinzhou Feng Shi Tang Xiaolin Yang Mengjie Zhang Zhizhong Li Shaoru Zhang Yongliang Han Yongmei Li Philippe P.Monnier Gang Yu Peng Zheng Cunjin Zhang Ke Xu Xinyue Qin 

机构地区：[1]Department of Neurology,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China [2]Department of Neurology,The People's Hospital of Tongliang District,Chongqing 402560,China [3]Department of Radiology,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China [4]Department of Physiology,Faculty of Medicine,University of Toronto,Toronto M5S 1A8,Canada [5]National Health Commission Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases,The First Affiliated Hospitalof Chongqing Medical University,Chongqing 400016,China [6]Department of Neurology,Sichuan Provincial People's Hospital,University of Electronic Science and Technology of China,Chengdu 611731,China

出　　处：《Science China(Life Sciences)》2025年第4期1042-1056,共15页中国科学(生命科学英文版)

基　　金：supported by the National Science Foundation of China (81701191, 82301720);Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0973, CSTB2023NSCQMSX0183, CSTB2023NSCQ-BHX0214);China Postdoctoral Science Foundation (2022M722384, 2023MD734128);the Joint Project of Chongqing Health Commission and Science and Technology Bureau (2020FYYX104);Chongqing Postdoctoral Special Support Foundation (2023CQBSHTB2010);Chongqing Postdoctoral Science Foundation (CSTB2023NSCQ-BHX0214);the First Affiliated Hospital of Chongqing Medical University Postdoctoral Science Foundation (CYYY-BSHPYXM-202310);CQMU Program for Youth Innovation in Future Medicine (W0168)。

摘　　要：Although disturbances in the gut microbiome have been implicated in multiple sclerosis(MS), little is known about the changes and interactions between the gut microbiome and blood metabolome, and how these changes affect disease-modifying therapy(DMT) in preventing the progression of MS. In this study, the structure and composition of the gut microbiota were evaluated using 16S rRNA gene sequencing and an untargeted metabolomics approach was used to compare the serum metabolite profiles from patients with relapsingremitting MS(RRMS) and healthy controls(HCs). Results indicated that RRMS was characterized by phase-dependent α-phylogenetic diversity and significant disturbances in serum glycerophospholipid metabolism. Notably, α-phylogenetic diversity was significantly decreased in RRMS patients during the chronic phase(CMS) compared with those in the acute phase(AMS). A distinctive combination of two elevated genera(Slackia, Lactobacillus) and five glycerophospholipid metabolism-associated metabolites(four increased: GPCho(22:5/20:3),PC(18:2(9Z,12Z)/16:0), PE(16:0/18:2(9Z,12Z)), PE(18:1(11Z)/18:2(9Z,12Z));one decreased: PS(15:0/22:1(13Z))) in RRMS patients when comparing to HCs. Moreover, a biomarker panel consisting of four microbial genera(three decreased: Lysinibacillus, Parabacteroides,UBA1819;one increased: Lachnoanaerobaculum) and two glycerophospholipid metabolism-associated metabolites(one increased: PE(P-16:0/22:6);one decreased: CL(i-12:0/i-16:0/i-17:0/i-12:0)) effectively discriminated CMS patients from AMS patients, which indicate correlation with higher disability. Additionally, DMTs appeared to attenuate MS progression by reducing UBA1819 and upregulating CL(i-12:0/i-16:0/i-17:0/i-12:0). These findings expand our understanding of the microbiome and metabolome roles in RRMS and may contribute to identifying novel diagnostic biomarkers and promising therapeutic targets.

关 键 词：relapsing remitting multiple sclerosis gut microbiota 16S rRNA gene sequence untargeted metabolomics lipid metabolism biomarker 

分 类 号：R744.5[医药卫生—神经病学与精神病学]