title: Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease.
abstract: 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.
  
  
  
  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,IRGMandFUT2.
  
  
  
  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 genusRoseburiain 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).
  
  
  
  We show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals.Roseburia sppare acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD.
authors: 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.
authors: Floris
authors: F
authors: Imhann
authors: 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.
authors: Arnau
authors: A
authors: Vich Vila
authors: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Marc Jan
authors: MJ
authors: Bonder
authors: Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Jingyuan
authors: J
authors: Fu
authors: Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.
authors: Dirk
authors: D
authors: Gevers
authors: 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.
authors: Marijn C
authors: MC
authors: Visschedijk
authors: 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.
authors: Lieke M
authors: LM
authors: Spekhorst
authors: 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.
authors: Rudi
authors: R
authors: Alberts
authors: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Lude
authors: L
authors: Franke
authors: Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Hendrik M
authors: HM
authors: van Dullemen
authors: Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Rinze W F
authors: RWF
authors: Ter Steege
authors: Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.|Biostatistics Department, Harvard School of Public Health, Boston, Massachusetts, USA.
authors: Curtis
authors: C
authors: Huttenhower
authors: Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Gerard
authors: G
authors: Dijkstra
authors: Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.|Massachusetts General Hospital, Boston, Massachusetts, USA.
authors: Ramnik J
authors: RJ
authors: Xavier
authors: 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.
authors: Eleonora A M
authors: EAM
authors: Festen
authors: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Cisca
authors: C
authors: Wijmenga
authors: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Alexandra
authors: A
authors: Zhernakova
authors: Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Rinse K
authors: RK
authors: Weersma
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D064806:Dysbiosis / Q000150:complications / Q000235:genetics / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment / Q000379:methods; D012720:Severity of Illness Index
keywords: BACTERIAL INTERACTIONS; GENETICS; INFLAMMATORY BOWEL DISEASE; INTESTINAL BACTERIA