Identification of early fine-scale microbial signatures in inflammatory bowel disease
Final Report Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive system, which includes Crohn’s disease (CD) and ulcerative colitis (UC) as its main subtypes, affecting in sum around 3.6 million people worldwide. Several observations from international human studies point towards the gut microbiome as an important intermediate phenotype, which plays an important role in regulating several metabolic and physiological functions and that is essential for gut health, being almost as important as any other human organ given its comparably metabolic activity and relevance. Though occurrence of IBD is known to correlate with reduced species richness and differential abundance of several bacterial taxa, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. To improve our understanding of microbial and/or metabolic disease causes, this study aimed to investigate microbiome changes in incident individuals within a huge and well characterized prospective cohort from Kiel, for which as well samples from probands with high risk for the disease (i.e., firstdegree relatives of IBD-patients) are available. By shotgun-metagenome sequencing of stool samples from roughly 150 CD and 150 UC index patients as well as 600 first-degree relatives and more than 1,000 healthy controls we were able to determine microbial diversity changes on the strain-level. During the time of the proposed project, a highly effective metagenomic pipeline was established within our research group that was used for pre-processing the data (github.com/ikmb/metagenomic-workflows) and enabled identification of over- and underrepresented microbial members in IBD patients. As has been described before, general microbial diversity was significantly lower in both subtypes compared to healthy controls. Though we could demonstrate a general increase of Proteobacteria in both subtypes, we observed significant differences in the abundances of Firmicutes (lower numbers in CD) and Bacteroidetes (lower numbers in UC), strongly arguing for differential microbial changes in both. We also observed a significant decrease of methanoarchaea within both subtypes, which was confirmed in a small subset by using an amplicon-based approach for specific detection of archaea. Since metagenomic reads contained relatively low amounts of fungal reads, but revealed some evidence for differential abundance of Candida species, we additionally performed quantitative Real-time PCR and thereby confirmed a significant higher abundance of C. tropicalis in UC patients. In summary, this project enabled extensively deeper insights into the microbial community and its dysbiosis in IBD patients compared to healthy controls with a particular focus on understudied microbial members such as fungi and archaea.
Publications
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Long‐Term Dietary Effects on Human Gut Microbiota Composition Employing Shotgun Metagenomics Data Analysis. Molecular Nutrition & Food Research, 67(24).
Troci, Alba; Rausch, Philipp; Waschina, Silvio; Lieb, Wolfgang; Franke, Andre & Bang, Corinna
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MAGScoT: a fast, lightweight and accurate bin-refinement tool. Bioinformatics, 38(24), 5430-5433.
Rühlemann, Malte Christoph; Wacker, Eike Matthias; Ellinghaus, David & Franke, Andre
