英夫利昔单抗联合酪酸梭菌对克罗恩病炎症及肠屏障的影响  

Influence of infliximab combined with Clostridium butyricum on inflammation and intestinal barrier function in Crohn′s disease

作　　者：施嫣红[1] 黄林生[3] 沈通一[2,3] 王俊珊[1] 刘占举[1] SHI Yan-hong;HUANG Lin-sheng;SHEN Tong-yi;WANG Jun-shan;LIU Zhan-ju(Gastroenterology,Shanghai Tenth People′s Hospital,Tongji University Medical School,Shanghai 200072,China;不详)

机构地区：[1]同济大学附属第十人民医院消化内科,上海200072 [2]同济大学附属第十人民医院胃肠外科,上海200072 [3]同济大学医学院肠道疾病研究所

出　　处：《中国微生态学杂志》2021年第12期1420-1424,共5页Chinese Journal of Microecology

基　　金：上海市卫生计生委资助项目(201640159);北京医卫健康公益基金项目(YWJKJJHKYJJ-A712)。

摘　　要：目的观察英夫利昔单抗(IFX)联合酪酸梭菌对克罗恩病(CD)患者炎症及肠屏障功能的影响。方法共纳入44例轻至中度CD患者随机分组,剔除3例,剩余观察组21例及对照组20例。对照组给予IFX治疗(第0,2,6,14,22和30周,5 mg/kg,注射一次),观察组在此基础上口服酪酸梭菌(40mg,一天三次),疗程30周。评估治疗后两组患者肠屏障功能、炎症活动指数及肠道菌群的差异。结果治疗后两组克罗恩病炎症活动指数(CDAI)、C-反应蛋白(CRP)、血沉(ERP)及血内毒素水平、尿乳果糖/甘露醇(L/M)比值均比治疗前明显下降(P<0.05),且观察组炎症指数显著低于对照组(P<0.05),观察组内毒素及尿L/M比值的下降较对照组明显(P<0.05)。治疗后观察组的菌群Shannon指数和Simpson指数均明显高于对照组(P<0.05)。在门水平,与对照组比较,观察组变形菌门(Proteobacteria)的丰度明显降低,拟杆菌门(Bacteroidetes)丰度明显升高(P<0.05);在属水平,观察组埃希菌属/志贺菌属(Escherichia/Shigella)丰度明显降低(P<0.05),阿利斯特杆菌属(Diali-ster)、相位弧菌属(Phascolarctobacterium)、粪杆菌属(Faecalibacterium)等丰度升高(P<0.05)。通过LEfSe分析发现观察组特征性菌群为梭菌纲(c_Clostridia)、梭菌目(o_Clostridiales)、瘤胃球菌科(f_Ruminococcaceae)、g_Erysipelotrichaceae incertae sedis、纺锤链杆属(g_Fusicatenibacter)、柯林斯菌(g_Collinsella)、摩根氏菌属(g_Morganella)、红蝽杆菌目(o_Coriobacteriales)、红蝽菌科(f_Coriobacteriaceae)、丹毒丝菌纲(c_Erysipelotrichia)、韦荣球菌科(f_Erysipelotrichaceae)和丹毒丝菌目(o_Erysipelotrichales),对照组为颗粒链菌属(g_Granulicatella)、肉杆菌科(f_Carnobacteri-aceae)。结论IFX联合酪酸梭菌可有效改善轻中度CD患者的菌群及肠黏膜屏障功能,并且可降低克罗恩病患者的炎症活动指数。Objective To observe the effect of infliximab combined with Clostridium butyricum on intestinal barrier function and therapeutic effects in patients with Crohn′s disease(CD).Methods A total of 44pa-tients with mild to moderate CD were randomly divided into observation group(n=21;5 mg/kg IFX at weeks 0,2,6,14,22and 30,combined with Clostridium butyricum)or control group(n=20;infliximab alone)respectively;3patients were excluded.The clinical activity index,intestinal barrier function,and gut flora were analyzed and compared between groups after 30 weeks of treatment.Results The levels of CDAI,C-reactive protein,ESR and serum endotoxin and ratio of urine lactulose/mannitol(L/M)in the two groups were significantly lower than those before treatment(P<0.05)respectively.The inflammatory in-dex in the observation group decreased more significantly than that in the control group(P<0.05),and the falling of endotoxin and urinary L/M ratio in the observation group was also more obvious than that in the control group(P<0.05).After treatment,the diversity of bacteria(Shannon index and Simpson index)in the observation group was significantly better than that in the control group(P<0.05).Compared with the control group,the abundance of Proteobacteria decreased while that of Bacteroidesincreased in the observa-tion group at the level of phylum(P<0.05).At genus level,the abundance of Escherichia/Shigella de-creased significantly,while that of Dialister,Phascolarctobacteriumand Faecalibacteriumincreased signifi-cantly in the observation group(P<0.05).The characteristic flora in the observation group were c_Clos-tridia,o_Clostridiales,f_Ruminococcaceae,g_Erysipelotrichaceaseincertaesedis,g_Fusicatenibacter,g_Collinsella,g_Morganella,o_Coriobacteriales,f_Coriobacteriaceae,c_Erysipelotrichia,f_Erys-ipelotrichaceae and o_Erysipelotrichales,while those in the control group were g_Granulicatella and f_Carnobacteriaeae through LEfSe analysis.Conclusion Infliximab combined with Clostridium butyricum can effectively improve the microflora

关 键 词：克罗恩病 英夫利昔单抗 酪酸梭菌 肠道菌群 肠黏膜屏障 

分 类 号：R969.4[医药卫生—药理学]