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

炎症性肠病早期精细微生物特征的鉴定

• 批准号: 433152305
• 负责人: Dr. Corinna Bang
• 金额: --
• 依托单位: Institut für Klinische Molekularbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/433152305?language=en
• 关键词: Identification; early; fine; scale; microbial

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.

为了确定预测炎症性肠病（IBD）临床发病或病程的分子特征，我们建立了一项基于家庭的前瞻性队列研究，反复收集IBD患者及其亲属的医学信息和生物样本。目前有超过1000人参与了这项研究，其中包括超过450名克罗恩病和溃疡性结肠炎的指数患者以及他们（尚未）未受影响的亲属，由于IBD的家族聚类和高遗传性，他们本身就处于患病的高风险中。为了进行比较，我们有来自100 000名健康对照者（来自同一地理区域的献血者）和51名treatment-naïve新诊断的IBD患者的粪便样本。粪便微生物群是IBD的重要中间表型，在之前的分析中，我们已经通过成本效益高的基于扩增子的16S rDNA基因测序确定了几个与IBD相关的粪便细菌分类群。由于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采用高分辨率宏基因组鸟枪测序来功能表征肠道微生物组。拥有元基因组霰弹枪数据，我们将能够(i)更好地量化粪便样本中的微生物物种，（ii）测量菌株水平上的多样性，（iii）识别可能与IBD相关的可能罕见的“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。