title: Pouch Inflammation Is Associated With a Decrease in Specific Bacterial Taxa.
abstract: OBJECTIVE
  Pouchitis is a common long-term complication in patients with ulcerative colitis (UC) undergoing proctocolectomy with ileal pouch-anal anastomosis. Because the inflammation occurs in a previously normal small bowel, studies of this process might provide information about the development of Crohn's disease. Little is known about the intestinal microbiome of patients with pouchitis. We investigated whether specific bacterial populations correlate with the pouch disease phenotype and inflammatory activity.
  
  
  METHODS
  We performed a prospective study of patients with UC who underwent pouch surgery (N = 131) from 1981 through 2012 and were followed at Tel Aviv Medical Center. Patients were assigned to groups based on their degree and type of pouch inflammation. Patients with familial adenomatous polyposis after pouch surgery (n = 9), individuals with intact colons undergoing surveillance colonoscopy (n = 10), and patients with UC who did not undergo surgery (n = 9) served as controls. We collected demographic and disease activity data (based on the Pouchitis Disease Activity Index) and measured levels of C-reactive protein. Fecal samples were collected, levels of calprotectin were measured, and microbiota were analyzed by 16S ribosomal RNA gene amplicon pyrosequencing.
  
  
  RESULTS
  Increased proportions of the Fusobacteriaceae family correlated with increased disease activity and levels of C-reactive protein in patients with UC who underwent pouch surgery. In contrast, proportions of Faecalibacterium were reduced in patients with pouchitis vs controls; there was a negative correlation between proportion of Faecalibacterium and level of C-reactive protein. There was an association between antibiotic treatment, but not biologic or immunomodulatory therapy, with reduced proportions of 11 genera and with increased proportions of Enterococcus and Enterobacteriaceae.
  
  
  CONCLUSIONS
  Reductions in protective bacteria and increases in inflammatory bacteria are associated with pouch inflammation in patients with UC who underwent pouch surgery. The finding that antibiotics exacerbate dysbiosis indicates that these drugs might not provide long-term benefit for patients with pouchitis. Additional studies of this form of dysbiosis could provide information about the pathogenesis of Crohn's disease.
authors.affiliation: Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Leah
authors.initials: L
authors.lastname: Reshef
authors.affiliation: Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel; IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Kovacs
authors.affiliation: IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel.
authors.forename: Amos
authors.initials: A
authors.lastname: Ofer
authors.affiliation: IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Yahav
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel.
authors.forename: Nitsan
authors.initials: N
authors.lastname: Maharshak
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology and Hepatology, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Nirit
authors.initials: N
authors.lastname: Keren
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology and Hepatology, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Fred M
authors.initials: FM
authors.lastname: Konikoff
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Colorectal Unit, Department of Surgery, Tel Aviv Medical Center, Tel Aviv, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Tulchinsky
authors.affiliation: Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. Electronic address: urigo@tauex.tau.ac.il.
authors.forename: Uri
authors.initials: U
authors.lastname: Gophna
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel. Electronic address: irisd@tlvmc.gov.il.
authors.forename: Iris
authors.initials: I
authors.lastname: Dotan
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D001419:Bacteria / Q000145:classification* / Q000187:drug effects / Q000235:genetics; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000601:surgery*; D039021:Colonic Pouches / Q000009:adverse effects*; D064806:Dysbiosis / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology*; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000032:analysis; D007557:Israel; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D019449:Pouchitis / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology*; D016737:Proctocolectomy, Restorative / Q000009:adverse effects*; D011446:Prospective Studies; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D021521:Ribotyping; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D007155:Immunologic Factors; D018836:Inflammation Mediators; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D002097:C-Reactive Protein
keywords: Gut Microbiota; IBD; Immune Regulation; Intestine