title: Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells.
abstract: BACKGROUND
  Probiotics have anti-inflammatory effects in patients with inflammatory bowel disease and appear to regulate mucosal immune response through reductions in proinflammatory cytokines. The probiotic VSL#3 prevents pouchitis if started within a week of ileostomy closure and maintains remission following antibacterial treatment in patients with refractory or recurrent pouchitis. However, the efficacy of probiotics and their effects on regulatory cells if started at a greater time after surgery in patients undergoing ileal pouch anal anastomosis (IPAA) for ulcerative colitis are unknown.
  
  
  METHODS
  We conducted an open-label study in which 31 patients at different periods from surgery without signs and symptoms of pouchitis were randomized to 2 sachets of VSL#3 once daily or no treatment for 12 months. Pouchitis disease activity index (PDAI) was evaluated at baseline and after 3, 6, and 12 months. The percentage of CD4+ T lymphocytes expressing CD25 and the inactive form of transforming growth factor-beta [latency-associated peptide (LAP)] were evaluated at baseline and after 3 and 6 months in peripheral-blood mononuclear cells and mucosal biopsies. Variation in tissue interleukin-1beta and Foxp3 mRNA expression was also evaluated.
  
  
  RESULTS
  During the study period, VSL#3-treated patients showed a significant reduction in PDAI score and a significant increase in the percentage of mucosal CD4+CD25(high) and CD4+ LAP-positive cells compared with baseline values. Tissue samples at different points showed a significant reduction in IL-1beta mRNA expression, and a significant increase in Foxp3 mRNA expression.
  
  
  CONCLUSIONS
  We conclude that VSL#3 administration in patients with IPAA modulates the PDAI and expands the number of mucosal regulatory T cells.
authors.affiliation: Department of General Surgery, P. Stefanini, University La Sapienza, Roma, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Pronio
authors.forename: Chiara
authors.initials: C
authors.lastname: Montesani
authors.forename: Cinzia
authors.initials: C
authors.lastname: Butteroni
authors.forename: Simona
authors.initials: S
authors.lastname: Vecchione
authors.forename: Gloria
authors.initials: G
authors.lastname: Mumolo
authors.forename: AnnaRita
authors.initials: A
authors.lastname: Vestri
authors.forename: Domenico
authors.initials: D
authors.lastname: Vitolo
authors.forename: Monica
authors.initials: M
authors.lastname: Boirivant
mesh_terms: D000328:Adult; D001003:Anal Canal / Q000601:surgery*; D000714:Anastomosis, Surgical / Q000009:adverse effects / Q000379:methods; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003093:Colitis, Ulcerative / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D039021:Colonic Pouches; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007778:Lactobacillus; D008297:Male; D008875:Middle Aged; D019449:Pouchitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D019936:Probiotics / Q000627:therapeutic use*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053583:Interleukin-1beta; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger