Gastroenterology

Gastroenterology

Volume 149, Issue 3, September 2015, Pages 718-727
Gastroenterology

Original Research
Full Report: Basic and Translational—Alimentary Tract
Pouch Inflammation Is Associated With a Decrease in Specific Bacterial Taxa

https://doi.org/10.1053/j.gastro.2015.05.041Get rights and content

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.

Section snippets

Patients and Controls

Pouch patients were recruited at the Comprehensive Pouch Clinic of the Tel Aviv Medical Center, a tertiary referral center for IBD and the national referral center for pouch patients. Both an IBD-oriented gastroenterologist (I.D.) and a colorectal surgeon (H.T.) routinely examine all patients. Study inclusion criteria included confirmed precolectomy diagnosis of UC (based on clinical, endoscopic, histologic, and imaging criteria), a minimum of 12 months follow-up after ileostomy closure, and at

Results

A total of 140 pouch patients (131 UC and 9 FAP) were recruited and followed-up during a period of 18 months (Table 1). The UC pouch patients included 38 with a normal pouch, 46 with acute or recurrent-acute pouchitis, 37 with chronic pouchitis/CLDP, and 10 whose classification changed during the study. For the major part of this study, only samples obtained from patients who had not been exposed to antibiotics in the month preceding sample procurement were used (antibiotic-free patients, n =

Discussion

Microbial dysbiosis is a term widely used to describe imbalances in gut microbiota associated with disease. Reductions in bacterial diversity and in the genus Faecalibacterium are the hallmarks of dysbiosis in IBD. In addition, a reduction in Bacteroides and in multiple taxa of the Lachnospiraceae and Ruminococcaceae had been described in ileal CD, but not in UC. In this study, we focused on UC patients after pouch surgery, specifically on the comparison between those developing pouch

References (46)

  • A. Kohyama et al.

    Bacterial population moves toward a colon-like community in the pouch after total proctocolectomy

    Surgery

    (2009)
  • D.M. Melville et al.

    Surgery for ulcerative colitis in the era of the pouch: the St Mark's Hospital experience

    Gut

    (1994)
  • R.D. Hurst et al.

    Prospective study of the incidence, timing and treatment of pouchitis in 104 consecutive patients after restorative proctocolectomy

    Arch Surg

    (1996)
  • B. Shen et al.

    Clinical approach to diseases of ileal pouch-anal anastomosis

    Am J Gastroenterol

    (2005)
  • P.H. Harper et al.

    Split ileostomy and ileocolostomy for Crohn's disease of the colon and ulcerative colitis: a 20 year survey

    Gut

    (1983)
  • L.A. Garcia Rodriguez et al.

    Acute gastroenteritis is followed by an increased risk of inflammatory bowel disease

    Gastroenterology

    (2006)
  • J. Qin et al.

    A human gut microbial gene catalogue established by metagenomic sequencing

    Nature

    (2010)
  • C. Manichanh et al.

    Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach

    Gut

    (2006)
  • U. Gophna et al.

    Differences between tissue-associated intestinal microfloras of patients with Crohn's disease and ulcerative colitis

    J Clin Microbiol

    (2006)
  • D.N. Frank et al.

    Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases

    Proc Natl Acad Sci U S A

    (2007)
  • H. Sokol et al.

    Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients

    Proc Natl Acad Sci U S A

    (2008)
  • H. Sokol et al.

    Low counts of Faecalibacterium prausnitzii in colitis microbiota

    Inflamm Bowel Dis

    (2009)
  • G.W. Tannock et al.

    Comprehensive analysis of the bacterial content of stool from patients with chronic pouchitis, normal pouches, or familial adenomatous polyposis pouches

    Inflamm Bowel Dis

    (2012)
  • Cited by (70)

    View all citing articles on Scopus

    Conflicts of interest The authors disclose no conflicts.

    Funding This study was partially supported by a generous grant from the Leona M. and Harry B. Helmsley Charitable Trust.

    Author names in bold designate shared co-first authorship.

    Authors share co-first authorship.

    View full text