不同疾病活动度溃疡性结肠炎患者肠道菌群变化及其与体液免疫和炎症反应的相关性

Changes of intestinal flora in patients with ulcerative colitis of different disease activities and its correlation with humoral immunity and inflammatory response

目的分析不同疾病活动度溃疡性结肠炎(UC)患者肠道菌群变化及与体液免疫、炎症反应的相关性,探讨肠道菌群变化在UC疾病活动中的作用。方法选择我院消化科2022年2月至2023年6月收治的78例UC患者为观察组,另选择我院同期健康体检者30例为对照组。采集所有受试者的粪便样本和外周静脉血样本,检测肠道菌群、血清体液免疫和炎症反应指标。对比观察组不同疾病活动程度患者的肠道菌群、体液免疫指标和炎症反应指标与对照组的差异,采用Pearson相关性分析UC患者肠道各菌群数量与疾病活动度、血清体液免疫和炎症反应指标的相关性,采用受试者工作特征曲线(ROC)分析肠道各菌群数量对UC的预测价值。结果观察组患者肠道大肠埃希菌、肠球菌、肠杆菌数量均高于对照组(t=8.879、15.379、17.181,均P<0.05),乳杆菌、双歧杆菌数量均低于对照组(t=20.807、21.656,均P<0.05);且观察组患者随疾病活动度的上升其大肠埃希菌、肠球菌、肠杆菌数量增加(F=16.524、77.880、129.410,均P<0.05),乳杆菌、双歧杆菌数量减少(F=179.970、86.859,均P<0.05)。观察组患者血清免疫球蛋白M(IgM)、免疫球蛋白A(IgA)、免疫球蛋白G(IgG)均低于对照组(t=19.627、9.435、4.037,均P<0.05),血清高迁移率族蛋白B1(HMGB1)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平均高于对照组(t=37.617、25.565、31.246,P<0.05);且观察组患者随疾病活动度的上升其血清HMGB1、IL-6、TNF-α水平上升(F=392.050、236.530、186.030,均P<0.05),IgM、IgG、IgA水平降低(F=25.340、13.151、59.954,均P<0.05)。相关性分析显示,UC患者大肠埃希菌、肠球菌、肠杆菌与血清IgG、IgM、IgA水平均呈负相关(r=−0.301、−0.312、−0.314、−0.306、−0.342、−0.355、−0.314、−0.348、−0.337,均P<0.05),与血清HMGB1、IL-6、TNF-α和Mayo评分呈正相关(r=0.301、0.363、0.326、0.365、0.379、0.471、0.469、0.421、0.402、0.374、0.453、0.389,均P<0.05);乳杆菌、双歧杆菌与血清IgG、IgM、IgA水平均呈正相关(r=0.292、0.375、0.413、0.303、0.348、0.474,均P<0.05),与血清HMGB1、IL-6、TNF-α和Mayo评分均呈负相关(r=−0.419、−0.386、−0.425、−0.421、−0.426、−0.473、−0.431、−0.373,均P<0.05)。ROC曲线分析显示,大肠埃希菌、肠球菌、肠杆菌、乳杆菌、双歧杆菌数量和联合检测对UC均有预测效能(Z=2.059、2.258、2.662、2.850、3.722、3.701,均P<0.05),其中联合检测的效能最高,其AUC为0.742,敏感性为96.15%,特异性为53.33%。结论UC患者存在显著的肠道菌群紊乱,且疾病活动度越高菌群紊乱越严重。肠道菌群紊乱与患者体液免疫、炎症反应相关,提示临床治疗时需重视肠道菌群的调节。

Objective To analyze the changes of intestinal flora in patients with ulcerative colitis(UC)of different disease activities and the correlation with humoral immunity and inflammatory response,and explore the role of intestinal flora changes in UC disease activity.Methods A total of 78 patients with UC admitted to department of gastroenterology of the hospital from February 2022 to June 2023 were selected as observation group,and 30 healthy physical examination subjects during the same period were included in control group.Fecal and peripheral venous blood samples were collected to detect the intestinal flora,serum humoral immunity and inflammatory response indicators.The differences in intestinal flora,humoral immunity indicators and inflammatory response indicators were compared among patients with different disease activities in observation group.Pearson correlation analysis was used to analyze the correlation of intestinal flora count with disease activity,serum humoral immunity and inflammatory response indicators in patients with UC.Receiver operating characteristic curve(ROC)was applied to analyze the predictive value of intestinal flora count on UC.Results The counts of Escherichia coli,Enterococcus and Enterobacter in observation group were higher(t=8.879,15.379,17.181;all P<0.05)while those of Lactobacillus and Bifidobacterium were lower than those in control group(t=20.807,21.656;all P<0.05),respectively.With the increase of disease activity in observation group,the counts of Escherichia coli,Enterococcus and Enterobacter increased(F=16.524,77.880,129.410;all P<0.05)while those of Lactobacillus and Bifidobacterium decreased(F=179.970,86.859;all P<0.05).Serum immunoglobulin M(IgM),immunoglobulin A(IgA)and immunoglobulin G(IgG)in observation group were lower(t=19.627,9.435,4.037;all P<0.05)while serum high mobility group protein B1(HMGB1),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were higher than those in control group(t=37.617,25.565,31.246;all P<0.05).With the increase of disease activity in observation group,serum HMGB1,IL-6 and TNF-αenhanced(F=392.050,236.530,186.030;all P<0.05)while IgM,IgG and IgA reduced(F=25.340,13.151,59.954;all P<0.05).Correlation analysis showed that Escherichia coli,Enterococcus and Enterobacter in patients with UC were negatively correlated with serum levels of IgG,IgM and IgA(r=−0.301,−0.312,−0.314,−0.306,−0.342,−0.355,−0.314,−0.348,−0.337;all P<0.05),and positively correlated with serum HMGB1,IL-6,TNF-αand Mayo score(r=0.301,0.363,0.326,0.365,0.379,0.471,0.469,0.421,0.402,0.374,0.453,0.389;all P<0.05).Lactobacillus and Bifidobacterium were positively correlated with serum levels of IgG,IgM and IgA(r=0.292,0.375,0.413,0.303,0.348,0.474;all P<0.05),and negatively correlated with serum HMGB1,IL-6,TNF-αand Mayo score(r=−0.419,−0.386,−0.425,−0.421,−0.426,−0.473,−0.431,−0.373;all P<0.05).ROC curve analysis revealed that Escherichia coli,Enterococcus,Enterobacter,Lactobacillus,Bifidobacterium and combined detection had predictive efficiency on UC(Z=2.059,2.258,2.662,2.850,3.722,3.701;all P<0.05),and the combined detection had the highest efficiency,with AUC of 0.742,sensitivity of 96.15%and specificity of 53.33%.Conclusion Patients with UC have obvious intestinal flora disturbance,and the higher the disease activity,the more severe the disturbance.Moreover,intestinal flora disturbance is related to humoral immunity and inflammatory response of patients,suggesting that the regulation of intestinal flora should be paid attention to in clinical treatment.