益生菌在犬異位性皮膚炎之機制探討

Abstract

流行病學調查指出，過去二十年間，「異位性皮膚炎」的發生率及普及率在已開發國家大幅提升。已知此疾病的成因除了受基因調控外與西化的生活型態有密切關係，環境因子更是誘發此疾病的關鍵。研究顯示，體內正常的微生物菌叢在免疫調控與平衡上扮演重要的角色。由於衛生環境的改善、飲食習慣的改變以及抗生素廣泛使用等因素，大幅降低接觸外在微生物菌叢的機會，因此也提高了罹患免疫失衡疾病的機率。益生菌的免疫調節能力在動物與人體實驗上已被證實，但其調控的機轉仍待研究。本次報告內容是探討納豆菌（Bacillus subtilis var. natto）如何透過調控體內的免疫反應進而達到抑制臨床上犬異位性皮膚炎的症狀。本實驗室透過蛋白質體學的分析，發現犬隻在攝入108cfu/ml納豆菌（Bacillus subtilis var. natto），可誘發免疫細胞活化，進而抑制體內載脂蛋白A-I(Apolipoprotein A-I)的表現。藉由較低濃度的載脂蛋白A-I，可進一步維持或放大納豆菌所引發的促發炎現象，而達到抗過敏的效果。研究結果顯示納豆菌（Bacillus subtilis var. natto）可刺激免疫細胞活化進而影響載脂蛋白A-I的表現，並且分泌相關免疫調控蛋白來維持適當之免疫發炎反應以達到對急性期異位性皮膚炎之治療效果。

Atopic dermatitis (AD) is one of the most common skin diseases that affects children and adults worldwide and its prevalence has been steadily increasing during the past decades. According to the hygiene hypothesis, the decreased exposure of microorganism results in altered T helper cells balance, increasing prevalence and severity of AD. Therefore, probiotics, with their important immune-regulatory potential, has been regarded as a novel strategy for the intervention of atopic disease. In this study, the probiotics, Bacillus subtilis var. natto, has been used for alleviating the symptoms of AD in clinical canine patients. After more than 3 weeks of treatment, the plasma samples were withdrawn from the dogs with significant clinical improvement to execute the proteomics analysis. After the statistical and comparative analysis, we have pinpointed that the down-regulation of apolipoprotein A-I (apoA-I), might get involved in the molecular mechanism mediated by Bacillus subtilis var. natto. Our studies have demonstrated that Bacillus subtilis var. natto could regulate the expression of apoA-I by its immunostimulatory activities and the down-regulation of apoA-I might play roles in the enhancement of its stimulatory effects. Furthermore, we also identified some immunoregulatory proteins, anexin-1, galectin-3 and thromospondin-1 might contribute to anti-AD effects supported by probiotics.