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Canadian Journal of Gastroenterology
Volume 22, Issue 3, Pages 237-242
Original Article

VSL#3 Probiotic Upregulates Intestinal Mucosal Alkaline Sphingomyelinase and Reduces Inflammation

Isaac Soo,1 Karen L Madsen,1 Qassim Tejpar,1 Beate C Sydora,1 Richard Sherbaniuk,1 Benedetta Cinque,2 Luisa Di Marzio,3 Maria Grazia Cifone,2 Claudio Desimone,2 and Richard N Fedorak1

1Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
2Department of Experimental Medicine, University of L’Aquila, L’Aquila, Italy
3Department of Drug Science, University G D’Annunzio, Chieti, Italy

Received 2 December 2006; Accepted 22 October 2007

Copyright © 2008 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


BACKGROUND: Alkaline sphingomyelinase, an enzyme found exclusively in bile and the intestinal brush border, hydrolyzes sphingomyelin into ceramide, sphingosine and sphingosine-1-phosphate, thereby inducing epithelial apoptosis. Reduced levels of alkaline sphingomyelinase have been found in premalignant and malignant intestinal epithelia and in ulcerative colitis tissue. Probiotic bacteria can be a source of sphingomyelinase.

OBJECTIVE: To determine the effect of VSL#3 probiotic therapy on mucosal levels of alkaline sphingomyelinase, both in a mouse model of colitis and in patients with ulcerative colitis.

METHODS: Interleukin-10 gene-deficient (IL10KO) and wild type control mice were treated with VSL#3 (109 colony-forming units per day) for three weeks, after which alkaline sphingomyelinase activity was measured in ileal and colonic tissue. As well, 15 patients with ulcerative colitis were treated with VSL#3 (900 billion bacteria two times per day for five weeks). Alkaline sphingomyelinase activity was measured through biopsies and comparison of ulcerative colitis disease activity index scores obtained before and after treatment.

RESULTS: Lowered alkaline sphingomyelinase levels were seen in the colon (P=0.02) and ileum (P=0.04) of IL10KO mice, as compared with controls. Treatment of these mice with VSL#3 resulted in upregulation of mucosal alkaline sphingomyelinase activity in both the colon (P=0.04) and the ileum (P=0.01). VSL#3 treatment of human patients who had ulcerative colitis decreased mean (± SEM) ulcerative colitis disease activity index scores from 5.3±1.8946 to 0.70±0.34 (P=0.02) and increased mucosal alkaline sphingomyelinase activity.

CONCLUSION: Mucosal alkaline sphingomyelinase activity is reduced in the intestine of IL10KO mice with colitis and in humans with ulcerative colitis. VSL#3 probiotic therapy upregulates mucosal alkaline sphingomyelinase activity.