干燥综合征患者肠道菌群的变化

Changes of intestinal flora in patients with Sjögren's syndrome

目的分析黑龙江省干燥综合征(Sjogren's syndrome,SS)患者的肠道菌群特征,为SS的诊疗提供新的证据和方向。方法收集2018年1月至2018年12月在哈尔滨医科大学附属第一医院风湿免疫科就诊的14例SS患者(SS组)和14名在本院体检的健康人(对照组)的粪便并提取粪便中细菌的DNA,扩增16S片段后测序,对测序结果进行生物信息分析。结果SS患者与正常人肠道菌群的丰度(Sobs,Chao,Ace)、谱系多样性(Pd)、菌落的多样性(Shannon,Simpson)和均匀度(Heip)均无显著差异(P>0.05)。SS患者肠道菌群中5个菌门,11个菌科和37个菌属与正常人存在着明显的差异。与正常对照组相比,在门水平上,SS患者肠道菌群中厚壁菌门,放线菌门和Saccharibacteria 3个菌门明显减少,拟杆菌门和变形菌门2个菌群明显增加,组间差异具有统计学意义(Z值分别为-4.27,-3.01,-2.57,-4.27和-2.53,P值均<0.05);在科水平上,SS患者肠道菌群中的拟杆菌科,产碱菌科、短杆菌科、柄杆菌科和诺卡氏菌科5个菌科明显增多,组间差异具有统计学意义(Z值分别为-4.09,-3.06,-2.41,-2.11和-2.11,P值均<0.05);而毛螺菌科、双歧杆菌科、红蝽菌科、拟杆菌目s24-7组、放线菌科和芽孢杆菌目XI菌科6个菌科明显减少,组间差异具有统计学意义(Z值分别为-3.17,-2.92,-3.40,-2.05,-2.05和-2.22,P值均<0.05);在属水平上,SS患者肠道菌群中拟杆菌属、Parabacteroides、瘤胃球菌科无分类信息的菌属、Parasutterella、短杆菌属、短波单胞菌属、Hungatella、Sellimonas和红球菌属明显增加,组间差异具有统计学意义(Z值分别为-4.09,-2.32,-2.03,-2.02,-2.41,-2.11,-2.16,-2.11,-2.11,P值均<0.05)。结论肠道菌群在不同的疾病中起到了相同、相似甚至相反的作用而且与人种和地域相关,拟杆菌属,布劳特氏菌属和双歧杆菌属可以对SS患者与健康人进行鉴别。

Objective To analyze the characteristics of intestinal flora in patients with Sjogren's Syndrome(SS)in Heilongjiang Province,in order to provide new evidence and direction for the diagnosis and treatment of SS.Methods The feces of 14 patients with SS(SS group)in the Department of Rheumatology and Immunology in the First Affiliated Hospital of Harbin Medical University from January 2018 to December 2018 were collected.At the same time,14 healthy people(control group)who underwent physical examination in our hospital were also collected.The bacterial DNA in the feces of the two groups was extracted and the 16S fragment was amplified and sequenced.The sequencing results were analyzed by bioinformatics.Results There was no significant difference in the abundance of intestinal flora(Sobs,Chao,Ace),pedigree diversity(Pd),colony diversity(Shannon,Simpson)and evenness(Heip)between SS patients and normal controls(P>0.05).There were significant differences in 5 phyla,11 families and 37 genera of intestinal flora between SS patients and normal controls.Compared with the normal control group,there were 3 phyla of Firmicutes,Actinobacteria and Saccharibacteria decreased significantly,and 2 flora of Bacteroidetes and Proteobacteria increased significantly in intestinal flora of SS patients at phyla level(Z values were-4.27,-3.01,-2.57,-4.27 and-2.53 respectively,all P values<0.05).At the family level,five families of Bacteroideaceae,Alcaligenaceae,Brevibacteriaceae,Caulobacteraceae and Nocardiaceae increased significantly(Z values were-4.09,-3.06,-2.41,-2.11 and-2.11 respectively,all P values<0.05),and six families of Lachnospiraceae,Bifidobacteriaceae,Coriobacteriaceae,Bacteroidales_S24-7_group,Actinomycetaceae,norank_p_Saccharibacteria,Family_XI_o_Bacillales decreased significantly in the intestinal flora of SS patients(Z values were-3.17,-2.92,-3.40,-2.05,-2.05 and-2.22 respectively,all P values<0.05).At the genus level,Bacteroides,Parabacteroides,norank_f_Ruminococcaceae,Parasutterella,Brevibacterium,Brevundimonas,Hungatella,Sellimonas,Rhodococcus increased significantly in intestinal flora of SS patients compared with the control group(Z values were-4.09,-2.32,-2.06,-2.02,-2.41,-2.11,-2.16,-2.11 and-2.11 respectively,all P values<0.05).Conclusion Intestinal flora plays the same,similar or even opposite role in different diseases,which is also related to race and region.Bacteroides,Blautia and Bifidobacterium can distinguish SS patients from healthy people.