益生菌 Lactobacillus casei Shirota 對 imiquimod 誘發乾癬小鼠之免疫調節的影響

Abstract

根據台灣健保資料庫數據顯示，乾癬就診人數逐年攀升。乾癬 (psoriasis) 為一種免疫失衡的慢性皮膚疾病。近年研究顯示，乾癬患者的腸道菌相多樣性較低，益生菌數量顯著減少。已知乳酸菌代田株 (Lactobacillus casei Shirota, LcS) 具有調節腸道菌組成與免疫調節的功能，但對於乾癬免疫調節的影響尚未研究。故本研究欲探討補充代田菌是否能減緩Imiquimod (IMQ) 誘發乾癬小鼠的發炎症狀。實驗設計將8週齡小鼠分為Control組、IMQ組、LcS/IMQ組、正控制組。於LcS/IMQ組小鼠的飲用水每天加入1 x 109 CFU/ml LcS 4週後，分別於小鼠12、20、26週齡時，進行連續5天背部皮膚與耳朵塗抹IMQ誘發乾癬，Ctrl組塗抹凡士林。於第三次誘發乾癬後將小鼠犧牲，分析免疫相關指標。結果顯示，LcS/IMQ組第一、二次誘發乾癬背部皮膚的皮屑程度與促發炎細胞激素IL-22與IL-6含量顯著較IMQ組低，且調節型細胞激素IL-10含量顯著較IMQ組高，顯示，LcS可能具有減緩皮膚發炎反應的能力。LcS/IMQ組的MLN細胞分泌IL-17A、TNF-α，以及脾臟細胞分泌IL-17A顯著低於IMQ組，IFN-γ的分泌顯著高於IMQ組，顯示，LcS可能具有減緩乾癬腸道與全身性發炎反應的能力。LcS/IMQ組腸道的Bifidobacterium菌含量趨勢性高於IMQ組，顯示，LcS可促進腸道益生菌的生長。綜合以上結果，推測補充代田菌藉由促進腸道益生菌生長與降低腸道促發炎細胞激素，進而影響全身性的免疫反應，降低脾臟分泌促發炎細胞激素，促進IFN-γ分泌，使T細胞偏向發育Th1，降低Th17細胞激素的分泌，並降低皮膚中促發炎細胞激素的含量，從而減緩乾癬的症狀。

The prevalence of psoriasis in Taiwan has increased year by year. Psoriasis is a T-cell-mediated chronic inflammatory skin disorder. Recently, accumulating evidence has supported the pathogenic role of the gut microbiome in autoimmune and inflammatory diseases, including psoriasis. It has been demonstrated that Lactobacillus casei Shirota (LcS) can prevent pathogen colonization of the gut and reduce the incidence or relieve the symptoms of various diseases caused by dysregulated immune responses. However, influence of LcS on psoriasis remains unknown. Therefore, this study was designed to investigate whether LcS could affect commensal microbiota and intestinal immunity on Imiquimod (IMQ)-induced psoriasis-like model. Eight weeks old mice were pretreated with probiotic LcS for 4 weeks, followed by receiving IMQ on the shaved back to induce psoriasis, and continuously given LcS until mice were sacrificed. The mice received a topical application of 62.5 mg IMQ cream or vaseline on the back skin daily for 5 consecutive days. The age induction of psoriasis was 12, 20, and 26 week-old, respectively. Here, the results showed that oral administration of LcS significantly decreased scaling lesions during the first and second induction of psoriasis compared to the IMQ group. It also reduced the cytokine production of proinflammatory cytokines, including IL-22 and IL-6, and increased IL-10 in the back skin of imiquimod-treated mice. LcS supplements significantly decreased gut proinflammatory cytokines, including IL-17A and TNF-α in IMQ-induced psoriasis-like mice. Meanwhile, cytokines IL-17A produced by ConA-stimulated splenocyte was reduced, increasing the secretion of IFN-γ. Furthermore, the gut microbiota in cecum contents from IMQ-induced psoriasis-like mice fed LcS increased the population of Bifidobacterium. In conclusion, oral administration of LcS could affect the immune responses and the gut microbiota compositions, which might be beneficial for amelioration progression of psoriasis.