Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells.
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.
Pronio
Annamaria
A
Department of General Surgery, P. Stefanini, University La Sapienza, Roma, Italy.
Montesani
Chiara
C
Butteroni
Cinzia
C
Vecchione
Simona
S
Mumolo
Gloria
G
Vestri
AnnaRita
A
Vitolo
Domenico
D
Boirivant
Monica
M
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
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053583:Interleukin-1beta; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger