Pouch Inflammation Is Associated With a Decrease in Specific Bacterial Taxa

BACKGROUND & AIMS: 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.