title: The probiotic VSL#3 has anti-inflammatory effects and could reduce endoscopic recurrence after surgery for Crohn's disease.
abstract: OBJECTIVE
  Probiotic formulations of single species of bacteria have not been effective in preventing the recurrence of Crohn's disease after surgery. We investigated the ability of VSL#3, a mixture of 8 different bacterial probiotic species, to prevent Crohn's disease recurrence after surgery in a multicenter, randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  Within 30 days of ileocolonic resection and re-anastomosis, patients with Crohn's disease were randomly assigned to groups given 1 sachet of VSL#3 (900 billion viable bacteria, comprising 4 strains of Lactobacillus, 3 strains of Bifidobacterium, and 1 strain of Streptococcus salivarius subspecies thermophilus) (n = 59) or matching placebo (n = 60). Colonoscopy was performed at days 90 and 365 to evaluate the neoterminal ileum for disease recurrence and obtain mucosal biopsies for cytokine analysis. Patients from both groups with either no or mild endoscopic recurrence at day 90 received VSL#3 until day 365. The primary outcome was the proportion of patients with severe endoscopic recurrence at day 90.
  
  
  RESULTS
  At day 90, the proportion of patients with severe endoscopic lesions did not differ significantly between VSL#3 (9.3%) and placebo (15.7%, P = .19). The proportions of patients with non-severe lesions at day 90 who had severe endoscopic recurrence at day 365 were 10.0% in the early VSL#3 group (given VSL#3 for the entire 365 days) and 26.7% in the late VSL#3 group (given VSL#3 from days 90 through 365) (P = .09). Aggregate rates of severe recurrence (on days 90 and 365) were not statistically different, 20.5% of subjects in the early VSL#3 group and 42.1% in the late VSL#3 group. Patients receiving VSL#3 had reduced mucosal inflammatory cytokine levels compared with placebo at day 90 (P < .05). Crohn's disease activity index and inflammatory bowel disease quality of life scores were similar in the 2 groups.
  
  
  CONCLUSIONS
  There were no statistical differences in endoscopic recurrence rates at day 90 between patients who received VSL#3 and patients who received placebo. Lower mucosal levels of inflammatory cytokines and a lower rate of recurrence among patients who received early VSL#3 (for the entire 365 days) indicate that this probiotic should be further investigated for prevention of Crohn's disease recurrence. Clinical trials.gov number: NCT00175292.
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: Richard.Fedorak@ualberta.ca.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Fedorak
authors.affiliation: Robarts Clinical Trials University of Western Ontario, London, Ontario, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Naomi
authors.initials: N
authors.lastname: Hotte
authors.affiliation: Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Des
authors.initials: D
authors.lastname: Leddin
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Levinus A
authors.initials: LA
authors.lastname: Dieleman
authors.affiliation: University of Victoria, Victoria, British Columbia, Canada.
authors.forename: Denis M
authors.initials: DM
authors.lastname: Petrunia
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Enns
authors.affiliation: McGill University, Montreal, Quebec, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Bitton
authors.affiliation: Guelph GI and Surgery Clinic, Guelph, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada.
authors.forename: Naoki
authors.initials: N
authors.lastname: Chiba
authors.affiliation: Université Laval, CHA-Hopitâl du Saint-Sacrement, Quebec City, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Paré
authors.affiliation: University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Alaa
authors.initials: A
authors.lastname: Rostom
authors.affiliation: McMaster University, Hamilton, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Marshall
authors.affiliation: Queen's University, Kingston, Ontario, Canada.
authors.forename: William
authors.initials: W
authors.lastname: Depew
authors.affiliation: University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Bernstein
authors.affiliation: University of Calgary, Calgary, Alberta, Canada.
authors.forename: Remo
authors.initials: R
authors.lastname: Panaccione
authors.affiliation: University of Montreal, Montreal, Quebec, Canada.
authors.forename: Guy
authors.initials: G
authors.lastname: Aumais
authors.affiliation: University of Toronto, Toronto, Ontario, Canada.
authors.forename: A Hillary
authors.initials: AH
authors.lastname: Steinhart
authors.affiliation: St John, New Brunswick, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Cockeram
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bailey
authors.affiliation: DIMEC University of Bologna, Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gionchetti
authors.affiliation: Robarts Clinical Trials University of Western Ontario, London, Ontario, Canada.
authors.forename: Cindy
authors.initials: C
authors.lastname: Wong
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Madsen
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001706:Biopsy; D003113:Colonoscopy; D003424:Crohn Disease / Q000517:prevention & control* / Q000601:surgery; D016207:Cytokines / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007082:Ileum / Q000473:pathology; D054444:Immunoglobulin Light Chains, Surrogate; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D019936:Probiotics / Q000008:administration & dosage*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D054444:Immunoglobulin Light Chains, Surrogate; D010919:Placebos
keywords: Bifidobacteria; IBDQ; Inflammatory Bowel Disease; Microbiota; Streptococcus; Treatment