重症肌无力病人肠道微生物群的变化  

Changes of intestinal microbiota in patients with myasthenia gravis

作　　者：赵明理[1] 曹建西[1] ZHAO Mingli;CAO Jianxi(Department of Cardiothoracic Surgery,The First Affiliated Hospital of He'nan University of Traditional Chinese Medicine,Zhengzhou,He'nan 450000,China)

机构地区：[1]河南中医药大学第一附属医院胸外科,河南郑州450000

出　　处：《安徽医药》2024年第8期1552-1557,共6页Anhui Medical and Pharmaceutical Journal

基　　金：河南省教育厅高等学校重点科研项目(20B360006);河南省中医药科学研究专项课题(2023ZY1006)。

摘　　要：目的探究重症肌无力(MG)病人和健康人群肠道微生物群的差异,以期为MG的诊断和治疗寻求新的途径。方法选择2021年8月至2022年12月河南中医药大学第一附属医院MG病人20例,健康志愿者10例,使用酶联免疫吸附(ELISA)测定MG病人和健康志愿者血清中细胞因子水平;通过Illumina MiSeq高通量测序仪检测MG病人和健康志愿者肠道微生物群多样性和结构的差异;通过OmicShare工具分析肠道微生物群与细胞因子[白细胞介素(IL)-6,IL-17,IL-22,IL-21,转化生长因子(TGF)-β,抗乙酰胆碱受体抗体(AChR)、人骨骼肌受体酪氨酸激酶抗体(MuSK)和人抗连接蛋白抗体(Titin)]之间的相关性。结果MG病人血液中IL-6,IL-17,IL-22,IL-21和TGF-β水平分别为(5.46±0.31)、(16.07±0.24)、(16.81±0.31)、(24.92±0.45)和(16613.00±247.80)ng/L,高于健康志愿者的(1.94±0.19)、(5.20±0.21)、(10.92±0.23)、(12.92±0.21)和(14462.00±140.70)ng/L,差异有统计学意义(P<0.01);而且,MG病人血液中的AChR、Musk和Titin抗体水平分别为(5.54±1.57)、(0.17±0.03)和(1.47±0.28)nmol/L,均高于健康志愿者的(0.75±0.20)、(0.03±0.02)和(0.19±0.04)nmol/L(P<0.05或P<0.01)。此外,MG病人肠道微生物的结构发生了较大改变,在门水平上,MG病人的拟杆菌门的相对丰度为(31.28±4.72)%低于健康志愿者的(55.61±5.47)%,差异有统计学意义(P<0.01),而增加了变形菌门的相对丰度(37.46±5.29)%比(33.24±3.36)%(P<0.01);在属水平上,MG病人的普雷沃菌属的相对丰度为(0.14±0.10)%低于健康志愿者的(24.01±9.90)%(P<0.01),而其志贺菌属的相对丰度为(12.92±5.21)%高于健康志愿者的(0.08±0.04)%(P<0.01);而且,关联分析结果显示志贺菌属与血清炎症因子呈显著正相关(P<0.05或P<0.01),普雷沃菌属和巨单胞菌属与血清炎症因子呈显著负相关(P<0.05或P<0.01),瘤胃球菌属和真细菌与AChR,MuSK和Titin等抗体水平呈正相关。结论MG病人和健康志愿者除了血清中细胞因子�Objective To explore the difference of intestinal microbiota between myasthenia gravis(MG)patients and healthy people,so as to find a new way for the diagnosis and treatment of MG.Methods A total of 20 MG patients and 10 healthy volunteers in the First Affiliated Hospital of He'nan University of Traditional Chinese Medicine from August 2021 to December 2022 were selected.The level of cytokines in the serum of MG patients and healthy volunteers by enzyme-linked immunosorbent assay(ELISA).The differences in diversity and structure of intestinal microbiota in patients with MG and healthy volunteers were detected by Illumina MiSeq high-throughput sequencer.The correlation between intestinal microbiota and cytokines[Interleukin(IL)-6,IL-17,IL-22,IL-21,transforming growth factor(TGF)-β,anti-acetylcholine receptor antibody(AChR),human skeletal muscle receptor tyrosine kinase antibody(MuSK),and human anti-connectin antibody(Titin)]was analyzed by OmicShare tool.Results The levels of inflammatory factors in blood of patients with MG were(5.46±0.31),(16.07±0.24),(16.81±0.31),(24.92±0.45)and(16613.00±247.80)ng/L,respectively,which were higher than those of healthy volunteers[(1.94±0.19),(5.20±0.21),(10.92±0.23),(12.92±0.21)and(14462.00±140.70)ng/L](P<0.01).Furthermore,the levels of AChR,Musk and Titin antibodies in the blood of patients with MG were(5.54±1.57),(0.17±0.03)and(1.47±0.28)nmol/L,respectively,which were higher than those of healthy volunteers[(0.75±0.20),(0.03±0.02)and(0.19±0.04)nmol/L](P<0.05 or P<0.01).In addition,the structure of intestinal microbiota in patients with MG has changed greatly.At the phyla level,the relative abundance of Bacteroides in MG patients was(31.28±4.72)%,which was lower than that in healthy volunteers(55.61±5.47)%,with a statistically significant difference(P<0.01),while the relative abundance of Proteobacteria in MG patients was higher than that in healthy volunteers[(37.46±5.29)%vs.(33.24±3.36)%](P<0.01).At the genus level,the relative abundance of Prevotella in

关 键 词：重症肌无力 菌群 免疫功能 志贺菌属 短链脂肪酸 

分 类 号：R746.1[医药卫生—神经病学与精神病学]