Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease.

Autor:	Imhann F; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Vich Vila A; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Bonder MJ; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Fu J; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Gevers D; Broad Institute of Harvard and MIT, Boston, Massachusetts, USA., Visschedijk MC; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Spekhorst LM; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Alberts R; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Franke L; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., van Dullemen HM; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Ter Steege RWF; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Huttenhower C; Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.; Biostatistics Department, Harvard School of Public Health, Boston, Massachusetts, USA., Dijkstra G; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Xavier RJ; Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.; Massachusetts General Hospital, Boston, Massachusetts, USA., Festen EAM; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Wijmenga C; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Zhernakova A; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Weersma RK; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Jazyk:	angličtina
Zdroj:	Gut [Gut] 2018 Jan; Vol. 67 (1), pp. 108-119. Date of Electronic Publication: 2016 Oct 08.
DOI:	10.1136/gutjnl-2016-312135
Abstrakt:	Objective: Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case-control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD. Design: Stool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2 , CARD9 , ATG16L1 , IRGM and FUT2 . Results: Strikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10 -13 ). Conclusions: We show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD. Competing Interests: Competing interests: None declared. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
Databáze:	MEDLINE
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