VSL#3 probiotic upregulates intestinal mucosal alkaline sphingomyelinase and reduces inflammation - PubMed (original) (raw)

VSL#3 probiotic upregulates intestinal mucosal alkaline sphingomyelinase and reduces inflammation

I Soo et al. Can J Gastroenterol. 2008 Mar.

Abstract

in English, French

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 (10(9) 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.

HISTORIQUE :: La sphingomyélinase alcaline, une enzyme contenue exclusivement dans la bile et la bordure en brosse intestinale, hydrolyse la sphingomyéline en céramide, en sphingosine et en sphingosine-1-phosphate, ce qui induit une apoptose épithéliale. On a trouvé des taux moins élevés de sphingomyélinase alcaline dans des épithéliums intestinaux précancéreux et cancéreux et dans des tissus de colite ulcéreuse. Les bactéries probiotiques peuvent être une source de sphingomyélinase.

OBJECTIF :: Déterminer l’effet de la thérapie probiotique VSL#3 sur les taux muqueux de sphingomyélinase alcaline, à la fois dans un modèle de souris atteinte de colite et chez des patients atteints de colite ulcéreuse.

MÉTHODOLOGIE :: Les auteurs ont traité des souris sans gène d’inter-leukine-10 (IL10KO) et des souris témoins de type sauvage au VSL#3 (109 unités formant des colonies par jour) pendant trois semaines, après lesquelles ils ont mesuré l’activité de la sphingomyélinase alcaline dans les tissus iléaux et coliques. De plus, ils ont traité 15 patients atteints de colite ulcéreuse au VSL 3 (900 milliards de bactéries deux fois par jour pendant cinq semaines). Ils ont mesuré l’activité de la sphingomyélinase alcaline au moyen de biopsies et de comparaisons entre les indices d’activité de la maladie avant et après le traitement.

RÉSULTATS :: Les auteurs ont observé des taux de sphingomyélinase alcaline moins élevés dans le côlon (P=0,02) et l’iléon (P=0,04) de souris IL10KO que ceux des sujets témoins. Le traitement de ces souris au moyen du VSL#3 a donné lieu à une régularisation positive de l’activité de la sphingomyélinase alcaline muqueuse à la fois dans le côlon (P=0,04) et l’iléon (P=0,01). Le traitement des patients humains atteints de colite ulcéreuse au VSL#3 a réduit les indices d’activité de la colite ulcéreuse moyens ±erreur-type de 5,3±1,8946 à 0,70±0,34 (P=0,02) et accru l’activité de la sphingomyélinase alcaline muqueuse.

CONCLUSION :: L’activité de la sphingomyélinase alcaline muqueuse est réduite dans l’intestin des souris IL10KO atteintes de colite et chez des humains atteints de colite ulcéreuse. La thérapie probiotique VSL#3 assure la régularisation positive de l’activité de la sphingomyélinase alcaline muqueuse.

PubMed Disclaimer

Figures

Figure 1)

Figure 1)

Mouse ileal mucosal alkaline sphingomyelinase activity. Placebo-fed interleukin-10 gene-deficient (IL10KO) mice (grey bar) demonstrated decreased ileal alkaline sphingomyelinase activity compared with placebo-fed wild type controls (hatched bar). Feeding VSL#3 (VSL Pharmaceuticals, Inc, USA) to IL10KO mice (solid bar) returned ileal alkaline sphingomyelinase activity to control levels. Values represent mean ± SEM for five to eight animals. *P=0.04 relative to placebo-fed wild type control mice; **P=0.01 relative to placebo-fed IL10KO mice

Figure 2)

Figure 2)

Mouse colonic mucosal alkaline sphingomyelinase activity. Placebo-fed interleukin-10 gene-deficient (IL10KO) mice (grey bar) demonstrated decreased colonic alkaline sphingomyelinase activity compared with placebo-fed wild type controls (hatched bar). Feeding VSL#3 (VSL Pharmaceuticals, Inc, USA) to IL10KO mice (solid bar) returned colonic alkaline sphingomyelinase activity to control levels. Values represent mean ± SEM for five to eight animals. *P=0.02 relative to placebo-fed wild type control mice; **P=0.04 relative to placebo-fed IL10KO mice

Figure 3)

Figure 3)

Mouse colonic histological injury score. Mouse histological injury score was increased in placebo-fed interleukin-10 gene-deficient (IL10KO) mice (grey bar) compared with IL10KO mice fed VSL#3 (VSL Pharmaceuticals, Inc, USA) (solid bar). Values represent mean ± SEM for six mice in each group. *P=0.02 relative to placebo-fed mice

Figure 4)

Figure 4)

Mouse colonic mucosal alkaline sphingomyelinase activity. VSL#3 (VSL Pharmaceuticals, USA)-fed wild type control mice demonstrated a fourfold increase in colonic mucosal alkaline sphin-gomyelinase activity compared with placebo-fed wild type controls. Values represent mean ± SEM for six animals. *P<0.05 relative to placebo-fed mice

Figure 5)

Figure 5)

Human colonic mucosal alkaline sphingomyelinase activity. Feeding VSL#3 (VSL Pharmaceuticals, Inc, USA) for five weeks to human patients with ulcerative colitis (solid bar) increased colonic mucosal alkaline sphingomyelinase activity relative to before therapy (grey bar). Values represent mean ± SEM for 15 subjects. *P=0.02 relative to before VSL#3 treatment

Figure 6)

Figure 6)

Ulcerative colitis disease activity index (UCDAI). The mean UCDAI score was reduced in human patients fed VSL#3 (VSL Pharmaceuticals, Inc, USA) for five weeks (solid bar) compared with before VSL#3 therapy (grey bar). Values represent mean ± SEM for 15 subjects. *P=0.02 relative to before VSL#3 treatment

Similar articles

Cited by

References

    1. Miyaji M, Jin ZX, Yamaoka S, et al. Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis. J Exp Med. 2005;202:249–59. - PMC - PubMed
    1. Ishii H, Takahashi T, Toyono M, et al. Acid sphingomyelinase deficiency: Cardiac dysfunction and characteristic findings of the coronary arteries. J Inherit Metab Dis. 2006;29:232–4. - PubMed
    1. Chatterjee S, Han H, Rollins S, Cleveland T. Molecular cloning, characterization, and expression of a novel human neutral sphingomyelinase. J Biol Chem. 1999;274:37407–12. - PubMed
    1. Duan RD, Cheng Y, Hansen G, et al. Purification, localization, and expression of human intestinal alkaline sphingomyelinase. J Lipid Res. 2003;44:241–50. - PubMed
    1. Duan RD, Hertervig E, Nyberg L, et al. Distribution of alkaline sphingomyelinase activity in human beings and animals. Tissue and species differences. Dig Dis Sci. 1996;41:1801–6. - PubMed

MeSH terms

Substances

LinkOut - more resources