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

• Published in: Gut Vol. 67; no. 1; pp. 108 - 119
• Main Authors: Imhann, Floris, Vich Vila, Arnau, Bonder, Marc Jan, Fu, Jingyuan, Gevers, Dirk, Visschedijk, Marijn C, Spekhorst, Lieke M, Alberts, Rudi, Franke, Lude, van Dullemen, Hendrik M, Ter Steege, Rinze W F, Huttenhower, Curtis, Dijkstra, Gerard, Xavier, Ramnik J, Festen, Eleonora A M, Wijmenga, Cisca, Zhernakova, Alexandra, Weersma, Rinse K
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 01.01.2018; BMJ Publishing Group LTD
• Subjects: Acetic acid; Adult; Antibiotics; Bacterial infections; BACTERIAL INTERACTIONS; Breastfeeding & lactation; Case-Control Studies; Colitis, Ulcerative - genetics; Colitis, Ulcerative - microbiology; Colitis, Ulcerative - pathology; Colon; Crohn Disease - genetics; Crohn Disease - microbiology; Crohn Disease - pathology; Crohn's disease; Dysbiosis - complications; Dysbiosis - genetics; Dysbiosis - microbiology; Endoscopy; Family medical history; Feces - microbiology; Female; Gastroenterology; Gastrointestinal Microbiome - genetics; Gene loci; Genetic diversity; Genetic Predisposition to Disease; GENETICS; Genomes; Gut microbiota; Host-Pathogen Interactions - genetics; Humans; Inflammation; INFLAMMATORY BOWEL DISEASE; Inflammatory bowel diseases; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - microbiology; Inflammatory Bowel Diseases - pathology; INTESTINAL BACTERIA; Intestinal microflora; Intestine; Male; Microbiota; Middle Aged; NOD2 protein; Pathogenesis; Peripheral blood; Phenotypes; Risk Assessment - methods; rRNA 16S; Severity of Illness Index; Netherlands; BACTERIAL INTERACTIONS; INFLAMMATORY BOWEL DISEASE; GENETICS; INTESTINAL BACTERIA
• ISSN: 0017-5749; 1468-3288; 1468-3288
• DOI: 10.1136/gutjnl-2016-312135

ObjectivePatients 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.DesignStool 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.ResultsStrikingly, 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).ConclusionsWe 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.