title: Fecal microbial composition of ulcerative colitis and Crohn's disease patients in remission and subsequent exacerbation.
abstract: BACKGROUND
  Limited studies have examined the intestinal microbiota composition in relation to changes in disease course of IBD over time. We aimed to study prospectively the fecal microbiota in IBD patients developing an exacerbation during follow-up.
  
  
  METHODS
  Fecal samples from 10 Crohn's disease (CD) and 9 ulcerative colitis (UC) patients during remission and subsequent exacerbation were included. Active disease was determined by colonoscopy and/or fecal calprotectine levels. Exclusion criteria were pregnancy, antibiotic use, enema use and/or medication changes between consecutive samples. The microbial composition was assessed by 16S rDNA pyrosequencing.
  
  
  RESULTS
  After quality control, 6,194-11,030 sequences per sample were available for analysis. Patient-specific shifts in bacterial composition and diversity were observed during exacerbation compared to remission, but overarching shifts within UC or CD were not observed. Changes in the bacterial community composition between remission and exacerbation as assessed by Bray-Curtis dissimilarity, were significantly larger in CD versus UC patients (0.59 vs. 0.42, respectively; p = 0.025). Thiopurine use was found to be a significant cause of clustering as shown by Principal Coordinate Analysis and was associated with decreases in bacterial richness (Choa1 501.2 vs. 847.6 in non-users; p<0.001) and diversity (Shannon index: 5.13 vs. 6.78, respectively; p<0.01).
  
  
  CONCLUSIONS
  Shifts in microbial composition in IBD patients with changing disease activity over time seem to be patient-specific, and are more pronounced in CD than in UC patients. Furthermore, thiopurine use was found to be associated with the microbial composition and diversity, and should be considered when studying the intestinal microbiota in relation to disease course.
authors.affiliation: School for Nutrition, Toxicology and Metabolism (NUTRIM), Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands; School for Nutrition, Toxicology and Metabolism (NUTRIM), Department of Medical Microbiology, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: Edgar S
authors.initials: ES
authors.lastname: Wills
authors.affiliation: School for Nutrition, Toxicology and Metabolism (NUTRIM), Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: Daisy M A E
authors.initials: DM
authors.lastname: Jonkers
authors.affiliation: School for Nutrition, Toxicology and Metabolism (NUTRIM), Department of Medical Microbiology, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Savelkoul
authors.affiliation: School for Nutrition, Toxicology and Metabolism (NUTRIM), Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: Ad A
authors.initials: AA
authors.lastname: Masclee
authors.affiliation: School for Nutrition, Toxicology and Metabolism (NUTRIM), Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: Marieke J
authors.initials: MJ
authors.lastname: Pierik
authors.affiliation: School for Nutrition, Toxicology and Metabolism (NUTRIM), Department of Medical Microbiology, Maastricht University Medical Center+, Maastricht, The Netherlands; School for Public Health and Primary Care (Caphri), Department of Epidemiology, Maastricht University, Maastricht, The Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: Penders
mesh_terms: D000328:Adult; D000368:Aged; D000963:Antimetabolites / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D003424:Crohn Disease / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D018450:Disease Progression; D005243:Feces / Q000382:microbiology; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007422:Intestines / Q000382:microbiology / Q000473:pathology; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use; D064307:Microbiota / Q000235:genetics*; D008875:Middle Aged; D011446:Prospective Studies; D012336:RNA, Ribosomal, 16S / Q000235:genetics*; D012008:Recurrence; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000963:Antimetabolites; D007155:Immunologic Factors; D012336:RNA, Ribosomal, 16S; D014409:Tumor Necrosis Factor-alpha; D015122:Mercaptopurine