A Disease-Associated Microbial and Metabolomics State in Relatives of Pediatric Inflammatory Bowel Disease Patients.
A Disease-Associated Microbial and Metabolomics State in Relatives of Pediatric Inflammatory Bowel Disease Patients.
复制标题
小儿炎症性肠病患者亲属中与疾病相关的微生物和代谢组学状态。
DOI：
10.1016/j.jcmgh.2016.06.004
复制
发表时间：
2016-11
影响因子：
7.2
通讯作者：
Dubinsky M
中科院分区：
文献类型：
--
作者：
Jacobs JP;Goudarzi M;Singh N;Tong M;McHardy IH;Ruegger P;Asadourian M;Moon BH;Ayson A;Borneman J;McGovern DP;Fornace AJ Jr;Braun J;Dubinsky M
微生物可能通过产生影响免疫活性和上皮功能的生物活性代谢物来增加炎症性肠病(IBD)的易感性。我们开展了一项以家庭为基础的研究，以确定IBD的微生物和代谢特征，当在健康的一级亲属中发现时，这些特征可能代表疾病前的风险状态。纳入21个儿童IBD家系，包括26例临床缓解的克罗恩病患者，10例临床缓解的溃疡性结肠炎患者，以及54名健康的兄弟姐妹/父母。采集粪便样本进行16S核糖体RNA基因测序、非靶向高效液相色谱-质谱仪代谢组学和钙保护素测定。使用Dirichlet多项式模型将个体分组为微生物和代谢组学状态。多变量模型被用来识别与这些状态相关的微生物和代谢物。将个体划分为2个微生物群落类型。一种与IBD有关，但与疾病状态无关，微生物多样性较低，微生物组成发生特征变化，包括肠杆菌科细菌增加，与生态失调相一致。在独立的儿科队列中，这种微生物群落类型与IBD和微生物多样性降低有类似的相关性。个体也以生物信息学的方式聚为两个具有共同粪便代谢组学特征的子集。一种代谢型与IBD有关，其特征是胆汁酸、牛磺酸和色氨酸增加。与IBD相关的微生物和代谢组学状态高度相关，表明它们代表着一个完整的生态系统。具有IBD相关微生物群落类型的健康亲属粪便钙保护素升高的发生率增加。健康的一级亲属可能会有与肠道代谢组改变相关的生物失调，这可能意味着疾病前的微生物易感状态或亚临床炎症。需要进行纵向前瞻性研究，以确定这些个体是否在临床上显著增加了发展为IBD的风险。
Microbes may increase susceptibility to inflammatory bowel disease (IBD) by producing bioactive metabolites that affect immune activity and epithelial function. We undertook a family based study to identify microbial and metabolic features of IBD that may represent a predisease risk state when found in healthy first-degree relatives. Twenty-one families with pediatric IBD were recruited, comprising 26 Crohn’s disease patients in clinical remission, 10 ulcerative colitis patients in clinical remission, and 54 healthy siblings/parents. Fecal samples were collected for 16S ribosomal RNA gene sequencing, untargeted liquid chromatography–mass spectrometry metabolomics, and calprotectin measurement. Individuals were grouped into microbial and metabolomics states using Dirichlet multinomial models. Multivariate models were used to identify microbes and metabolites associated with these states. Individuals were classified into 2 microbial community types. One was associated with IBD but irrespective of disease status, had lower microbial diversity, and characteristic shifts in microbial composition including increased Enterobacteriaceae, consistent with dysbiosis. This microbial community type was associated similarly with IBD and reduced microbial diversity in an independent pediatric cohort. Individuals also clustered bioinformatically into 2 subsets with shared fecal metabolomics signatures. One metabotype was associated with IBD and was characterized by increased bile acids, taurine, and tryptophan. The IBD-associated microbial and metabolomics states were highly correlated, suggesting that they represented an integrated ecosystem. Healthy relatives with the IBD-associated microbial community type had an increased incidence of elevated fecal calprotectin. Healthy first-degree relatives can have dysbiosis associated with an altered intestinal metabolome that may signify a predisease microbial susceptibility state or subclinical inflammation. Longitudinal prospective studies are required to determine whether these individuals have a clinically significant increased risk for developing IBD.