【作者】 李伟；

【导师】 雷光华；

【作者基本信息】 中南大学 ， 外科学， 2022， 硕士

【摘要】 目的:肠道菌群是人体最大且最具有代表性的微生物生态系统,既往研究提示肠道菌群在维系软骨健康中发挥着重要作用,但尚无研究探讨肠道菌群紊乱与软骨钙化症(chondrocalcinosis,CC)的相关性。本研究拟通过鸟枪法宏基因组测序,比较CC患者与正常对照组间肠道菌群的组成和功能变化。方法:本研究的研究对象源自一项大样本自然人群队列——湘雅骨关节炎研究。通过对研究对象膝关节、手关节以及髋关节拍摄X线片进行CC诊断:当关节内部出现明确的线状软骨钙化影时,可诊断为CC。规范化收集研究对象粪便样本,提取DNA后进行鸟枪法宏基因组测序,采用多元线性回归分析(multivariate linear regression analysis,Ma As Lin)等生物信息学分析方法,对CC患者与非CC患者之间肠道菌群的组成与功能差异进行比较。结果:本研究共纳入1,380名研究对象(平均年龄:63.2岁;女性占比:58.2%),CC的总体患病率为20%(n=276)。CC患者与对照组在肠道菌群基因水平、科水平、属水平和种水平上的α多样性(香农指数)无统计学差异;在基因水平、科水平和属水平上的β多样性(JSD距离)存在显著差异(P值分别为0.049,3.659e-08和1.576e-06,均P<0.05)。在菌种分类水平上,与对照组相比,CC患者的屎肠球菌(P=0.011,Q=0.103)、齿双歧杆菌(P=0.026,Q=0.170)、普雷沃氏菌sp900317685(P=0.027,Q=0.173)和MGYG.HGUT.00655(P=0.033,Q=0.192)的相对丰度较高;而共生梭菌(P=0.032,Q=0.189)和lavalense梭菌(P=0.032,Q=0.190)的相对丰度较低。CC患者与对照组相比,存在12种差异KEGG代谢通路,其中包括肌苷单磷酸生物合成(P=0.037,Q=0.165)和尿苷单磷酸生物合成(P=0.039,Q=0.169)在CC患者中的相对丰度显著升高。结论:CC患者存在肠道菌群紊乱,肠道菌种相对丰度改变和菌群相关功能变化可能与CC的发病机制相关。图5幅,表4个,参考文献55篇更多还原

【Abstract】 Objectives: The causality and pathogenic mechanism of microbiome composition remain elusive in chondrocalcinosis(CC).This study aimed to elucidate gut microbiome’s role in CC pathology and the relationship between the gut microbiota.Methods: Participants were from a community-based observational study conducted among the residents of the rural areas of China.Knee,hip or hand joint radiograph were obtained from each subject.Radiographic chondrocalcinosis was present if there was definite linear cartilage calcification.Gut microbiome was profiled by shotgun metagenomic sequencing and the microbial composition and function were determined.Results: The study sample included 1,380 participants(women:58.2%;mean age: 63.2 years;prevalence of CC: 20.0%).β-diversity indicated by JSD(genetic level: P=0.049;taxonomic level of family:P=3.659e-08;taxonomic level of genus: P=1.576e-06),but not α-diversity indicated by Shannon index(genetic level: P=0.299;taxonomic level of family: P= 0.361;taxonomic level of genus: P=0.381;taxonomic level of species: P=0.392),was significantly associated with prevalent CC.After adjusting for potential confounders,participants with CC had higher relative abundance of species Enterococcus＿B＿faecium,Bifidobacterium dentium,Prevotella sp900317685 and MGYG.HGUT.00655 than those without CC.Functional annotation analysis revealed that inosine monophosphate biosynthesis(P= 0.037,Q= 0.165)and Uridine monophosphate biosynthesis(P= 0.039,Q= 0.169)were enriched in participants with CC.Conclusions: This first population-based observational study utilizing metagenomic shotgun sequencing provides the empirical evidence that alterations of gut microbiome composition and function were observed among CC individuals.更多还原