Mucosa-Associated Microbiota and Risk of Chronic and/Or Relapsing Pouchitis After Restorative Proctocolectomy for Ulcerative Colitis
Marco Scarpa1, Alessia R. Grillo2, Anna Pozza*3, Diego Faggian4, Cesare Ruffolo5, Melania Scarpa2, Renata D'Incà3, Mario Plebani4, Giacomo C. Sturniolo3, Ignazio Castagliuolo2, Imerio Angriman3
1Department of Surgery, Veneto Oncological Institute (IOV-IRCCS), Padova, Italy; 2Dept. of Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy; 3Dept. of Surgical and Gastroenterological Sciences, University of Padova, Padova, Italy; 4Dept. of Diagnostic Sciences and Special Therapy, University of Padova, Padova, Italy; 5Dept. of Surgery (Chirurgia IV), Ospedale “Ca’ Foncello”, Treviso, Italy
Background Pouchitis can be classified as occasional or relapsing and about 5% of patients develops a chronic inflammatory condition. Chronic pouchitis can lead to the pouch failure. Aims of our study were to identify possible relationship between chronic/relapsing pouchitis and mucosa-associated microbiota, systemic and local inflammation, local cytokines network and toll like receptors expression. Patients and methods In this prospective study 32 consecutive patients who underwent restorative proctocolectomy, coming for follow up endoscopy in our out-patient department were recruited in 2007. Clinical disease activity was classified using Pouchitis Disease Activity Index. During pouch endoscopy biopsies from the ileal pouch were obtained to culture bacteria adherent to the mucosa and perform routine histology. Systemic inflammatory status was graded according to blood cell count, ESR, CRP, and albuminemia. Local inflammatory status was assessed with faecal lactoferrin levels analyzed by quantitative ELISA. Serum and mucosal levels of IL-1β, IL-6 and TNF-α were measured with immunometric assays. The mucosal expression of toll-like receptors for bacterial lipopolysaccharide (TLR4) and peptidoglycan (TLR2) were measured by quantitative Real Time RT-PCR. After a median follow up of 23 (IQR 20-24) months the patients were contacted for a reassessment of current and past disease activity. Univariate logistic regression, non parametric statistics and survival analysis were performed.Results Clinical diagnosis of pouchitis (PDAI>7) had been made in 10 patients in 2007. During the follow up 3 of these patients failed to recover and thus had chronic pouchitis while other 3 of them had relapsing episodes of pouchitis. In patients with chronic/relapsing pouchitis mucosal TLR2 and TLR4 were more expressed than in those with no or only one episode of pouchitis (p=0.036 and p=0.016, respectively). The number of CFU of mucosa-associated Clostridiaceae spp was higher in patients with chronic/relapsing pouchitis than in those with no or only one episode of pouchitis (p=0.031). The presence of Clostridiaceae spp adherent to the ileal mucosa was associated to a significant risk of chronic/relapsing pouchitis [OR: 14 (95% CI 0.887-224.021), p=0.045]. Survival analysis showed that the presence of Clostridiaceae spp was associated to earlier pouchitis relapse (p=0.019). Conclusion Chronic/relapsing pouchitis is associated to increased expression of mucosal TLR2 and TLR4. The populations of mucosa-associated Clostridiaceae spp seemed to play a role in the pathogenesis of chronic/relapsing pouchitis.
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