Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, PO box 80082, 3508 TB Utrecht, The Netherlands.
Respir Res. 2014 Apr 16;15(1):46. doi: 10.1186/1465-9921-15-46.
Asthma is estimated to affect as many as 300 million people worldwide and its incidence and prevalence are rapidly increasing throughout the world, especially in children and within developing countries. Recently, there has been a growing interest in the use of potentially beneficial bacteria for allergic diseases. This study is aimed at exploring the therapeutic effects of long-term treatment with two different beneficial bacterial strains (Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1) and a glucocorticoid (budesonide), as a reference treatment, on inflammatory response in a murine model for chronic allergic asthma.
To mimic the chronic disease in asthmatic patients, we used the murine ovalbumin-induced asthma model combined with prolonged allergen exposure. Airway function; pulmonary airway inflammation; airway remodelling, mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; mast cell degranulation; in vitro T cell activation; and expression of Foxp3 in blood Th cells were examined.
Lactobacillus rhamnosus reduced lung resistance to a similar extent as budesonide treatment in chronically asthmatic mice. Pulmonary airway inflammation, mast cell degranulation, T cell activation and airway remodelling were suppressed by all treatments. Beneficial bacteria and budesonide differentially modulated the expression of toll-like receptors (TLRs), nod-like receptors (NLRs), cytokines and T cell transcription factors. Bifidobacterium breve induced regulatory T cell responses in the airways by increasing Il10 and Foxp3 transcription in lung tissue as well as systemic by augmenting the mean fluorescence intensity of Foxp3 in blood CD4+ T cells.
These findings show that Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1 have strong anti-inflammatory properties that are comparable to budesonide and therefore may be beneficial in the treatment of chronic asthma.
据估计,哮喘影响着全球多达 3 亿人,其发病率和患病率在全球范围内迅速上升,尤其是在儿童和发展中国家。最近,人们对利用潜在有益细菌治疗过敏性疾病越来越感兴趣。本研究旨在探索长期使用两种不同有益细菌(短双歧杆菌 M-16V 和鼠李糖乳杆菌 NutRes1)和糖皮质激素(布地奈德)治疗对慢性过敏性哮喘小鼠模型炎症反应的治疗效果,作为参考治疗。
为了模拟哮喘患者的慢性疾病,我们使用了卵清蛋白诱导的哮喘小鼠模型结合延长的过敏原暴露。检测气道功能;肺部气道炎症;气道重塑;肺组织中模式识别受体、Th 特异性细胞因子和转录因子的 mRNA 表达;肥大细胞脱颗粒;体外 T 细胞激活;以及血液 Th 细胞中 Foxp3 的表达。
在慢性哮喘小鼠中,鼠李糖乳杆菌降低肺阻力的效果与布地奈德治疗相似。所有治疗均抑制肺部气道炎症、肥大细胞脱颗粒、T 细胞激活和气道重塑。有益细菌和布地奈德对 Toll 样受体(TLRs)、核苷酸结合寡聚化结构域样受体(NLRs)、细胞因子和 T 细胞转录因子的表达有不同的调节作用。短双歧杆菌通过增加肺组织中 Il10 和 Foxp3 的转录以及全身血 CD4+T 细胞 Foxp3 的平均荧光强度,在气道中诱导调节性 T 细胞反应。
这些发现表明,短双歧杆菌 M-16V 和鼠李糖乳杆菌 NutRes1 具有与布地奈德相当的强大抗炎特性,因此可能有益于慢性哮喘的治疗。