Identification of early fine-scale microbial signatures in inflammatory bowel disease

为了确定预测炎症性肠病(IBD)临床发病或病程的分子标志，我们建立了一项基于家族的前瞻性队列研究，重复收集IBD患者及其亲属的医学信息和生物样本。目前，超过1,000人参与了这项研究，其中包括450多名克罗恩病和溃疡性结肠炎的指标患者及其(尚未)未受影响的亲属，鉴于IBD的家族聚集性和高遗传性，他们本身就有很高的疾病发展风险。为了进行比较，我们从1000名健康对照(来自相同地理区域的献血者)和51名治疗初诊的IBD患者的粪便样本中获得。粪便微生物群是IBD的重要中间表型，在先前的分析中，我们通过使用基于扩增的16S rDNA基因测序，鉴定了几种与IBD相关的粪便细菌分类群。由于使用这种方法在物种水平上的分辨率有限，我们在这里的目标是通过使用高分辨率的元基因组鸟枪测序来描述肠道微生物组的功能特征。有了后基因组猎枪数据，我们将能够(I)更好地量化粪便样本中的微生物物种，(Ii)测量菌株水平的多样性，(Iii)确定可能与IBD有关的可能稀有的“指示物种”，以及(Iv)分析和功能表征非细菌成员，如真菌和古菌，但也特别关注病毒。

In order to identify molecular signatures that predict the clinical onset or course of inflammatory bowel disease (IBD), we established a family-based prospective cohort study with repeated collection of medical information and biosamples in IBD patients and their relatives. Currently, over 1,000 individuals are participating in this study, including more than 450 index patients with Crohn's disease and ulcerative colitis as well as their (yet) unaffected relatives, which are at high risk for developing the disease themselves, given the familial clustering and the high heritability of IBD. For comparison, we have stool samples available from >1,000 healthy controls (blood donors from the same geographical region) and from 51 treatment-naïve newly diagnosed IBD patients.The stool microbiome is an important intermediate phenotype for IBD and in prior analyses, we have identified several faecal bacterial taxa associated with IBD by using cost-efficient amplicon-based 16S rDNA gene sequencing. Since resolution on species level is limited using this method, we here aim to functionally characterize the intestinal microbiome by employing high-resolution metagenomic shotgun sequencing. Having metagenomic shotgun data at hands, we will be able (i) to better quantify microbial species in stool samples, (ii) to measure diversity on the strain-level, (iii) to identify probable rare “indicator species” that might be associated with IBD and to (iv) analyse and functionally characterize non-bacterial members such as fungi and archaea, but also with a particular focus on viruses.