Lactobacillus paracasei subsp. paracasei NTU 101 乳酸菌粉對 dextran sulfate sodium (DSS) 誘導小鼠結腸炎的改善效果

Abstract

發炎性腸道疾病 (inflammatory bowel disease, IBD) 可分為潰瘍性結腸炎 (ulcerative colitis) 和克隆氏症 (Crohn’s disease)，而其確切的致病原因仍不清楚，然而先天基因、免疫調控、環境因素及腸道的微生物皆可能造成 IBD 的產生，其中腸道微生物菌叢的擾亂已被認為是造成發炎性腸道疾病的主要致病因素之一。過去文獻指出某些乳酸菌可藉由活化樹突細胞而直接或間接去影響免疫系統的調節，因此在臨床上也出現以益生菌作為輔助性療法的概念。本實驗室分離之本土乳酸菌 Lactobacillus paracasei subsp. paracasei NTU 101 在過去的研究中已證實具有抗發炎和調節腸道菌相等功效，而這些因素也和 IBD 的某些致病機制有相關，因此本研究欲評估 NTU 101 菌粉對結腸炎小鼠的疾病改善效果。本研究誘導小鼠結腸炎所使用之葡聚醣硫酸鈉，為廣泛用來模擬結腸炎之一種模式。當葡聚醣硫酸鈉接觸到結腸時，會干擾結腸上皮腸蔽完整性、造成腸道通透性增加、引起連續慢性發炎反應及腸道出血。L. paracasei subsp. paracasei NTU 101 乳酸菌為一株經證實具多重功效之菌株，並評估 NTU 101 原末菌粉對腸炎小鼠的改善效果。將 2% 的葡聚醣硫酸鈉溶於小鼠的飲用水連續 7 天來誘導結腸炎，而將 5.0 × 108 CFU/kg BW/day的 NTU 101 菌粉持續餵食 25 天，並於誘導後開始觀察小鼠的每日疾病活動指數。結果顯示 NTU 101 菌粉能夠提升腸內抗氧化之能力、降低促發炎細胞激素、提升抗發炎細胞激素並稍微減緩小鼠於實驗後期數天內的體重下降，顯示在此葡聚醣硫酸鈉所誘導之結腸炎小鼠模式中能緩解其模擬之臨床症狀。

Inflammatory bowel diseases (IBDs) mainly consists of ulcerative colitis (UC) and Crohn’s disease (CD), and the pathogenesis of IBDs is still unclear. The interactions between immunologic, genetic, and environmental factors with intestinal microflora may contribute to the development of IBDs. However, imbalance of intestinal commensal microbiota is well-recognized as a pathogenic factors contributing to the development of IBDs. Since many previous studies have shown that some strains of lactic acid bacteria can directly or indirectly to influence the immunnoregulation through modulate and activate dentric cells, this concept that the use of probiotics could have some beneficial effect as the alternative therapy clinically had been extensively perfomed in clinical aspects. Lactobacillus paracasei subsp. paracasei NTU 101 has been proven to show anti-oxidative stress and anti-inflammatory effects in in vitro studies with the capacity to promote intestinal symbiosis and modulate immune responses in in vivo studies, and these factors has been identified to associate with pathogenesis of IBD. Consequently, this study determine the effect of NTU 101 on clinical symptoms, oxidative stress, and inflammation caused by colitis in mice. The murine colitis in this study was induced by the dextran sulfate sodium (DSS), which is one of the most commonly used animal model in colitis. When transited to the colon site in animal, DSS can interrupt the epithelial barrier function, lead to gut leakage, and finally elicit continuous chronic inflammation with intestinal bleeding. Lactobacillus paracasei subsp. paracasei NTU 101 is a proven multi-effect probiotic strain. In this study, the efficacy of Lactobacillus paracasei subsp. paracasei NTU 101 powder was studied against DSS-induced colitis in mice. Colitis was induced by 2.0% DSS in drinking water for 7 days and the mice were treated with 5.0 × 108 CFU/kg BW/day of the NTU 101 powder for 25 days, and after the induction of colitis, disease activity were monitored daily until the end of experiment. The results indicated that the NTU 101 powder improved anti-oxidant capacity, reduced pro-inflammatory cytokine level, increased the anti-inflammatory cytokine, and slightly ameliorated body weight loss in the DSS-treated mice during the last days in this study, which indicated that the NTU 101 powder can relieve clinical symptoms in DSS-induced colitis in mice.