重症肌无力患者肠道菌群及其代谢产物的变化
Altered gut microbiota and their metabolites in patients with myasthenia gravis
吴倩 1李君莲 2李海燕 2胡婉贞 2张晓燕2
作者信息
- 1. 中国人民解放军联勤保障部队第九四〇医院神经内科(兰州 730050);山东省菏泽市市立医院神经内科
- 2. 中国人民解放军联勤保障部队第九四〇医院神经内科(兰州 730050)
- 折叠
摘要
目的 探讨重症肌无力(myasthenia gravis,MG)患者肠道菌群及其代谢产物的变化.方法 收集MG患者及健康对照者的新鲜粪便标本,使用16S rRNA基因测序测定两组肠道菌群的丰度,并使用气相色谱质谱技术测定代谢产物的水平.收集受试者的临床特征,包括MG定量评分(quantitative MG score,QMGS)、MG日常生活活动能力量表(MG-activities of daily living,MG-ADL)评分、15项MG生活质量量表(MG-specific quality-of-life 15,MG-QOL-15)评分、徒手肌力评定量表(manual muscle testing,MMT)评分及乙酰胆碱受体抗体滴度水平,对差异菌群与临床特征的相关性进行分析.结果 研究共收集50例MG患者及15名健康对照者.MG组Simpson指数(0.936±0.041)高于对照组(0.888±0.123),即MG组Alpha多样性降低,差异有统计学意义(t=2.349,P=0.022),且两组的微生物表型即Beta多样性存在差异(R=0.966,P=0.001,Adonis).LEfSe结果提示MG组中志贺氏杆菌、琥珀酸弧菌属、梭杆菌属、瘤胃球菌属富集,而丰度降低的有毛螺菌属、罗氏菌属、脱硫弧菌属、粪球菌属.两组菌群的代谢产物不同,其中MG组有28种上调及71种下调代谢产物.京都基因与基因组百科全书功能聚类分析显示差异代谢产物主要参与代谢途径为氨基酸代谢、核苷酸代谢途径.MG患者肠道微生物61.2%(30/49)的扩增子序列(ampli-con sequence variant,ASV)与多种代谢产物相关(P<0.001).毛螺菌科与患者QMGS(r=-0.496,P<0.001)、MG-ADL评分(r=-0.542,P<0.001)、MG-QOL15评分(r=-0.464,P=0.007)、乙酰胆碱受体抗体滴度(r=-0.315,P=0.026)呈负相关,与MMT评分(r=0.374,P=0.008)呈正相关.结论 MG患者肠道菌群存在有益菌丰度下调,有害菌丰度上调的情况,亦存在代谢产物紊乱,且差异ASV与MG肌无力严重程度具有负相关.
Abstract
Objective This study investigated whether gut microbiota and its metabolites are altered in myasthenia gravis(MG)patients.Methods We collected fresh stool specimens from MG patients and healthy controls.16S rRNA gene sequencing and gas chromatography-mass spectrometry were used to measure abundance of gut microbiota and metabolite levels in two groups,respectively.Clinical data of the subjects were also collected including quantitative MG score(QMGS),MG-activities of daily living(MG-ADL),MG-specific quality-of-life 15(MG-QOL15),manual muscle testing(MMT),and the acetylcholine receptor antibody(AchR-Ab)titers.The correlation between the differential microbiota and the clinical characteristics was investigated.Results A total of 50 MG patients and 15 healthy controls were recruited.Simpson's index was significantly higher in the MG group(0.936±0.041)than in the control group(0.888±0.123).Alpha diversity was significantly decreased in the MG group(t=2.349,P=0.022).There was a significant difference in microbial phenotype between the two groups(R=0.966,P=0.001,Adonis).The results of LEfSe showed that the abundance of Esherichia-Shigella,Succinivibrio,Fusobacterium,and Ruminococcus-gnavus-group were up-regulated while the abundance of Lachnospira,Roseburia,Desulfovibrio,and Coprococcus were down-regulated.The results showed that the metabolites of the MG group were significantly different from those of the control group.There were 28 metabolites up-regulated and 71 metabolites down-regulated in the MG patient group.Kyoto Encyclopedia of Genes and Genomes analyses demonstrated that the majority of metabolic pathways in which differential metabolites were involved were related to amino acid metabolism and nucleotide metabolism.61.2% (30/49)of bacterial amplicon sequence variant(ASV)were significantly associated with multiple metabolites(P<0.001).The relative abundance of Lachnospiraceae in the group with MG was negatively correlated with the QMGS(r=-0.496,P<0.001),MG-ADL(r=-0.542,P<0.001),MG-QOL15(r=-0.464,P=0.007),and the AchR-Ab(r=-0.315,P=0.026).The relative abundance of Lachnospiraceae in the group with MG was positively correlated with the MMT(r=0.374,P=0.008).Conclusion The intestinal flora of MG patients is down-regulated in the abundance of beneficial bacteria and up-regulated in the abundances of harmful bacteria.Disturbance of metabolites are also present in MG patients.Regulating gut microbiota in MG patients may be a new target for treating the disease.
关键词
重症肌无力/肠道菌群/代谢产物/16S/rRNA/多样性/气相色谱质谱技术/相关性Key words
Myasthenia gravis/Gut microbiota metabolite/16Sr RNA/Diversity/Gas chromatography-mass spec-trometry/Correlation引用本文复制引用
基金项目
甘肃省自然科学基金(21JR11RA003)
兰州市科技计划项目(2023-ZD-175)
院内课题应用基础研究(2023YXKY007)
应用研究基础项目(2022yxky008)
出版年
2024
NETL
NSTL
万方数据