Dysbiosis and pouchitis

Grillo

Journal of Gastrointestinal Surgery

et al. 2012

Defensins are small cationic peptides with antibacterial activity expressed in Paneth cells (α-defensins) or generally in intestinal epithelial cells (β-defensins) that have a profound effect on gut microbiota. Chronic pouchitis, which occurs in 5% of patients after restorative proctocolectomy and can cause pouch failure, is associated to a significant increase of Clostridiaceae spp. The aim of this study was to gain further insight in the pathogenesis of pouch dysbiosis by exploring defensin expression. Thirty-two consecutive patients coming for follow-up endoscopy were recruited. On pouch biopsies, we cultured bacteria adherent to the mucosa and determined α- and β-defensins and toll-like receptor-4 and -2 mRNA by quantitative real-time RT-PCR. Serum and mucosal levels of IL-1β, IL-6 and TNF-α were measured with immunometric assays. Faecal lactoferrin was analysed by quantitative ELISA. After a median follow-up of 23 (IQR 20-24) months, the patients were contacted for a reassessment of current and past disease activity. During the follow-up, chronic/relapsing pouchitis was diagnosed in six patients. The mucosal level of α-5 and α-6 defensins correlated with chronic/relapsing pouchitis onset (τ = 0.30, p = 0.034 and τ = 0.28, p = 0.053, respectively). High levels of α-5 defensin resulted to be predictive of chronic/relapsing pouchitis [AUC = 74% (95% CI = 53-89%), p = 0.052]. Patients with high levels of α-5 and α-6 defensins had earlier pouchitis relapses (p = 0.009 and p = 0.034, respectively). High levels of α-5 defensin were associated to a significant risk of chronic/relapsing pouchitis [OR = 10.6 (95% CI = 1.2-97.6), p = 0.027]. At multivariate analysis, the mucosal levels of α-5 defensin and the number of CFU of mucosa-associated Clostridiaceae spp resulted to be independent predictors of chronic/relapsing pouchitis [β = 0.46 (0.18), p = 0.024 and β = 0.44 (0.18), p = 0.027, respectively]. In conclusion, chronic/relapsing pouchitis is associated to increased expression of mucosal HD-5 and to increased antimicrobial activity against Escherichia coli. In patients with chronic/relapsing pouchitis, HD-5 and TLR-4 over-expression is likely to create a hostile environment against Enterobacteriaceae, thus favouring Clostridiaceae spp by decreasing competing bacteria families.

Section: Introductionmentioning

confidence: 98%

Innate Immune Environment in Ileal Pouch Mucosa: α5 Defensin Up-regulation as Predictor of Chronic/Relapsing Pouchitis

Grillo

Journal of Gastrointestinal Surgery

et al. 2012

“…No single identifiable causative organism has been detected as the cause of pouchitis, but the infiltration of neutrophils and the proven response to antibacterial therapy suggest that pouchitis could have a bacterial cause [24][25][26][27] . However, different facts suggest that HCMV is a real gastrointestinal pathogen and that it can be partly related to the development of pouchitis in some patients.…”

Section: Discussionmentioning

confidence: 99%

Possible role of human cytomegalovirus in pouchitis after proctocolectomy with ileal pouch-anal anastomosis in patients with ulcerative colitis

Casadesús

Tani

Wakai³

et al. 2007

WJG

AIM:To detect the presence of human cytomegalovirus (HCMV) proteins and genes on the ileal pouch of patients with ulcerative colitis who have undergone proctocolectomy with ileal pouch-anal anastomosis (iPAA). METHODS:immunohistochemistry, polymerase chain reaction (PCR) and PCR sequencing methods were utilized to test the presence of HCMV in pouch specimens taken from 34 patients in 86 endoscopies. RESULTS:HCMV genes and proteins were detected in samples from 12 (35.2%) patients. The rate of detection was significant in the endoscopies from patients diagnosed with pouchitis (5 of 12, 41.6%), according to the Japanese classification of pouchitis, in comparison to patients with normal pouch (7 of 62, 11.2%; P = 0.021). in all patients with pouchitis in which the HCMV was detected, it was the first episode of pouchitis. The virus was not detected in previous biopsies taken in normal endoscopies of these patients. During the followup, HCMV was detected in one patient with recurrent pouchitis and in 3 patients whose pouchitis episodes improved but whose positive endoscopic findings persisted.CONCLUSION: HCMV can take part in the inflammatory process of the pouch in some patients with ulcerative colitis who have undergone proctocolectomy with iPAA.

“…Even with molecular microbiology techniques, no individual species or phylotype specifically associated with either UC or FAP pouchitis were found [44,47], and the role of bacterial diversity and dysbiosis in pouchitis is controversial [44,47,50]. It has been difficult to identify bacterial profiles unique for pouchitis with cross-sectional study design.…”

Section: Challengesmentioning

confidence: 99%

Bacteriology in the Etiopathogenesis of Pouchitis

Shen

2012

Dig Dis

Background: Pouchitis is the most common long-term complication in ulcerative colitis that follows restorative proctocolectomy. Clinical evidence suggests that dysbiosis plays a key role in its pathogenesis. Methods: Current literature on the topic was reviewed. A therapeutic approach was proposed based on the literature along with personal experience from the subspecialty Pouchitis Clinic. Results: Pouchitis represents a disease spectrum in the reservoir, with ranging etiopathogenesis, clinical phenotypes, disease courses and prognoses. Dysbiosis plays a critical role in disease initiation and progress, with antibiotic therapy as the mainstay for treatment. On the other hand, superimposed infection from pathogens contributes to flare-up of the disease. Pouchitis can progress into an ‘IBD-like’ condition, requiring anti-inflammatory, immunomodulator or even biological therapy. Conclusion: Pouchitis represents a unique form of IBD. Investigation on the evolution from an antibiotic-responsive phenotype to chronic antibiotic-refractory pouchitis may shed some light on the pathogenesis and therapeutic targets of IBD.