Soo I, Madsen K L, Tejpar Q, Sydora B C, Sherbaniuk R, Cinque B, Di Marzio L, Cifone M Grazia, Desimone C, Fedorak R N
Division of Gastroenterology, University of Alberta, Edmonton, Canada.
Can J Gastroenterol. 2008 Mar;22(3):237-42. doi: 10.1155/2008/520383.
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.
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.
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.
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.
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.
碱性鞘磷脂酶是一种仅存在于胆汁和肠道刷状缘的酶，它将鞘磷脂水解为神经酰胺、鞘氨醇和鞘氨醇-1-磷酸，从而诱导上皮细胞凋亡。在癌前和恶性肠道上皮以及溃疡性结肠炎组织中已发现碱性鞘磷脂酶水平降低。益生菌可能是鞘磷脂酶的一个来源。
确定VSL#3益生菌疗法对结肠炎小鼠模型和溃疡性结肠炎患者黏膜碱性鞘磷脂酶水平的影响。
用VSL#3（每天10⁹ 个菌落形成单位）治疗白细胞介素-10基因缺陷（IL10KO）小鼠和野生型对照小鼠3周，之后测量回肠和结肠组织中的碱性鞘磷脂酶活性。此外，15例溃疡性结肠炎患者接受VSL#3治疗（每天9000亿个细菌，分两次服用，共5周）。通过活检测量碱性鞘磷脂酶活性，并比较治疗前后获得的溃疡性结肠炎疾病活动指数评分。
与对照组相比，IL10KO小鼠结肠（P = 0.02）和回肠（P = 0.04）中的碱性鞘磷脂酶水平降低。用VSL#3治疗这些小鼠导致结肠（P = 0.04）和回肠（P = 0.01）中的黏膜碱性鞘磷脂酶活性上调。VSL#3治疗溃疡性结肠炎患者可使平均（±标准误）溃疡性结肠炎疾病活动指数评分从5.3±1.8946降至0.70±0.34（P = 0.02），并增加黏膜碱性鞘磷脂酶活性。
患有结肠炎的IL10KO小鼠肠道和患有溃疡性结肠炎的人类肠道中的黏膜碱性鞘磷脂酶活性降低。VSL#3益生菌疗法可上调黏膜碱性鞘磷脂酶活性。
