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Játtað í: 2019 Granskingarøki: Heilsa Verkætlanarslag: Verkætlan Verkætlanarheiti: Identifying the contribution of intestinal dysbiosis to Faroese IBD Risk Játtanarnummar: 0347 Verkætlanarleiðari: Amanda Gratton Vang Stovnur/virki: Heilsu- og Sjúkrarøkt á Fróðskaparsetrinum Aðrir luttakarar: Kári Rubek Nielsen, Jóngerð Midjord, Marjun á Frííðriksmørk Berbisá, Anna Cacilia Ingham, Johan Burisch, Noomi O. Gregersen Verkætlanarskeið: 01/08/2019-01/08/2021 Actial: 01/08/2019-31/12/2022 Samlaður kostnaður: 2.118.871 Stuðul úr Granskingargrunninum: 1.091.193 Verkætlanarlýsing: Original Inflammatory Bowel disease (IBD) is a group of chronic inflammatory diseases of the gastrointestinal tract that effects over 3 million peaple in Europa alone and plaves a high burden on societies and publicly funded health care systems like the Faroese. The underlying etiopathogenic factor(s) for IBD remain unclear, but it is generally accepted that IBD results from a complex relationship between genetic susceptibility, environment factors and intestinal microbiota. However, host genetics only explains a small fraction of disease heritability. There is a growing consensus that dysbiosis, especially a reduction in the diversity of the stool microbiome, is a hallmark of IBD. The prevalence of IBD on the Faroe Islands is the highest in the world (3-4 times higher than in other high-risk areas in North America and Europe) and the incidence rate has increased immensely over the last 20 years. The risk of developing IBD in Faroese individuals that move to Denmark in higher than native Danish people at arrival bit decreases over time, strongly suggesting the impact of environmental factors in the pathogenesis of IBD. Despite these unique features of the Faroese population and almost 1% of the population being affected by these diseases to date there has been limited focus on investigating the underlying reasons or the individual risk profiles of Faroese inhabitants. Such an effort will potentially enable personalized risk managment and ultimately even prevention of disease. This study will focus on the microbes found in stool samples from the Faroese IBD cohort and healthy controls in order to further understand the causal factor driving the high rate of IBD on the Faroe Islands. This is a crucial step in addressing an issue of utmost importance for the Faroese community. Research Question: Dysbiosis is considered a hallmark of IBD, however reports on specific taxa and associate with disease states vary. What characterizes dysbiosis in Faroese IBD patients? Aim: We will use a 16s rRNA sequencing approach in an exploratory study to investigate stool community composition in samples donated by Faroese IBD patients and Faroese healthy controls. Our primary outcomes will be principle component analysis of abundance and diversity measurments. Final The Dysbiosis in Faroese IBD project provided the first molecular data on Faroese intestinal health. Despite a small sample size, we were able to successfully complete the first part of the project which was to perform a cross-sectional study that compared the fecal microbiome of the healthy population with that of IBD (ulcerative colitis) patients. The results were published in Inflammatory Bowel Diseases, which is the official journal of the American Crohn’s and Colitis Foundation. One key finding from the cross-sectional study was that 30% of the healthy control population and 50% of the UC patients lacked verrucomicrobia, a protective phylum of bacteria whose absence has been associated with dysbiosis and dysregulated intestinal immune response in other studies. Of particular interest is a suggested association between genetic risk for metabolic dysfunction and lack of verrucomicrobia. Our working hypothesis is that the Faroese population has a “hidden” multifactor risk for developing inflammatory diseases which connects IBD, psoriasis, rheumatological, and metabolic diseases. This broad genetic risk combined with a shift toward industrialization is most likely driving the high rates of IBD within the Faroese population. Once the major goal of the project was satisfied with the publication of the cross-sectional study, we set out to establish the framework for performing a longitudinal study. In total, we collected 24 samples. The samples were prepared using the same laboratory and sequencing workflow that was developed for the cross-sectional study. However, the bioinformatics analysis was done using a bacterial sequencing pipeline that was developed by Ása Jacobsen and Ása Johannasen from Fiskaaling. The reason for this was to further develop Faroese competence in analyzing bacterial sequencing data and demonstrate transdisciplinary cooperation between Faroese projects. It is not possible to draw overall conclusions from the longitudinal dataset because of the small sample size. However, we do see signs of extreme dysbiosis in some of the samples if you compare the diversity to the results from the cross-sectional cohort. This is expected for people having active disease. One clear finding from the longitudinal dataset is that the lack of verrucomicrobia is a consistent hallmark within the Faroese microbiome and mirrors the results from the cross-sectional study. The lack of verrucomicrobia in both the Faroese IBD and health cohort may speak to an underlying immunological issue in the general population which is not currently being addressed by the Faroese research and health care community. Ideally, IBD should be viewed under a common umbrella with other immunological and perhaps metabolic disorders when it comes to providing holistic health care. Faroese drinking water quality should also be considered. The Faroese research council funded project on Cryptosporidium and Giardia (grant number 0455) showed high levels of both parasites in sewage. This is relevant to IBD because infection with the aforementioned parasites is a differential diagnosis for Ulcerative colitis and chronic re-infection with these parasites has been associated with risk for Irritable Bowel and Chronic fatigue syndrome. Støða: Liðug Avrik: Scientific articles, books, thesis etc. Berbisá M á F, Nielsen RK, Ingham AC, Midjord J, Hammer T, Patursson P, Vest NMO, Gregersen N, Burisch J, Vang A. Similar gut bacterial composition between patients with ulcerative colitis and healthy controls in a high incidence population: a cross-sectional study of the Faroe Islands IBD cohort. Inflammatory Bowel Diseases. 2022; Feb 9. DOI: 10.1093/ibd/izab355 Other results, such as unpublished articles, patents, computer systems, original models and new procedures Master´s thesis of Marjun Á Fríðriksmørk Berbisá, Department of Molecular Biology, University of Aarhus (2019). Storage and access rights to collected data The collected raw data and metadata is under the authority of the Genetic Biobank of the Faroe Islands. Participants must be reconsented to use the data for other study purposes. << Back |
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