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

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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.