炎症性肠病患者伴发泌尿系结石的相关因素及肠道菌群和代谢物特征分析

Risk factors and characteristics of gut microbiota and metabolites in inflammatory bowel diseases patients with urolithiasis

目的探讨炎症性肠病(IBD)患者伴发泌尿系结石的相关因素及肠道菌群和代谢物特征。方法回顾性连续纳入2014年1月至2019年12月在北京协和医院消化科就诊的IBD患者中伴发泌尿系结石者68例(结石组),按1∶2纳入性别和年龄匹配的不伴泌尿系结石者136例(非结石组)。泌尿系结石诊断依据腹部平片、泌尿系超声、腹部CT或静脉尿路造影。收集全部患者的临床相关资料,分析临床特征与泌尿系结石形成的相关性。测定其中10例结石组患者和18例非结石组患者粪便样本中微生物群落及代谢物构成。结果结石组男49例,女19例,年龄(36.0±12.4)岁;非结石组男98例,女38例,年龄(36.1±12.5)岁。单因素分析结果显示,克罗恩病(CD)患者中,结石组(n=34)既往行回肠造口术或小肠切除术的患者比例(26.5%比7.4%,P=0.019)和红细胞沉降率[26.5(12.0,40.8)比13.0(7.2,32.5)mm/1 h,P=0.022]高于非结石组(n=68)。溃疡性结肠炎(UC)患者中结石组(n=34)与非结石组(n=68)比较临床特征、生化指标差异均无统计学意义(均P>0.05)。多因素logistic回归分析结果显示,CD患者中,既往行回肠造口术或小肠切除术是结石形成的相关因素(OR=4.619,95%CI:1.178~18.111,P=0.028)。肠道菌群多样性方面,两组间α及β多样性差异均无统计学意义(均P>0.05)。在门水平上,两组肠道菌群丰度差异均无统计学意义(均P>0.05)。在属水平上,结石组肠球菌属(P=0.049)、挑剔真杆菌属(P=0.036)等丰度降低。在种水平上,结石组Bacteroides_coprocola丰度升高(P=0.035),Blautia_caecimuris(P=0.042)等丰度降低。两组间代谢产物差异均无统计学意义(均P>0.05)。线性判别(Lefse)分析显示,鞘脂单胞菌目、Fenollaria、粪居拟杆菌是结石组中对差异贡献显著的标志物种。结论既往行回肠造口术或小肠切除术是CD患者泌尿系结石形成的相关因素。肠道菌群可能参与IBD患者泌尿系结石的发生。

Objective To identify the related factors and characteristics of gut microbiota and metabolites in inflammatory bowel disease(IBD)patients with urolithiasis.Methods A total of 68 IBD patients with urolithiasis and 136 gender-and age-matched IBD patients without urolithiasis in the Department of Gastroenterology,Peking Union Medical College Hospital from January 2014 to December 2019 were recruited.The diagnosis of urolithiasis was confirmed by plain films,ultrasonography,abdominal computed tomography or intravenous urography.The clinical data of patients were collected,and the association between the clinical characteristics and urolithiasis was further analyzed.The fecal samples were collected from 10 patients with urolithiasis and 18 patients without urolithiasis,and the gut microbiota and metabolites composition were analyzed.Results There were 49 male and 19 female IBD patients with urolithiasis,with a mean age of(36.0±12.4)years,and 98 male and 38 female patients without urolithiasis,with a mean age of(36.1±12.5)years.Univariate analysis revealed that the rate of ileostomy and the resection of small intestine in Crohn′s disease(CD)patients with urolithiasis(n=34)was significantly higher than CD patients without urolithiasis(n=68)(26.5%vs 7.4%,P=0.019).And the erythrocyte sedimentation rate was also higher[26.5(12.0,40.8)vs 13.0(7.2,32.5)mm/1 h,P=0.022]in CD patients with urolithiasis.There were no significant differences in clinical characteristics and biochemical parameters between the ulcerative colitis(UC)patients with urolithiasis(n=34)and without urolithiasis(n=68)(all P>0.05).The multivariate logistic regression analysis indicated that ileostomy and the resection of small intestine were the independent related factors for urolithiasis in CD patients(OR=4.619,95%CI:1.178-18.111,P=0.028).There was no significant difference inαandβdiversity between the two groups(all P>0.05).At the phylum level,there was no significant difference in the abundance of microbiota(all P>0.05).At the genus level,the abundance of Enterococcus(P=0.049),Eubacterium_eligens(P=0.036)was significantly decreased.At the species level,the abundance of Bacteroides_coprocola was increased in urolithiasis group(P=0.035),while the abundance of Blautia_caecimuris was significantly decreased(P=0.042).No significant difference was found in fecal metabolites between the two groups(all P>0.05).According to LDA effect size(Lefse)analysis,taxa including Sphingomonadales,Fenollaria,Bacteroides_coprocola contributed greatly to the difference between the two groups.Conclusions Ileostomy and the resection of small intestine are related factors for urolithiasis in patients with CD.Gut microbiota may be involved in the occurrence of urolithiasis in patients with IBD.