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鼻腔内给予益生菌鼠李糖乳杆菌 GG 可预防小鼠变应性哮喘模型中的桦树花粉诱导的过敏。

Intranasal administration of probiotic Lactobacillus rhamnosus GG prevents birch pollen-induced allergic asthma in a murine model.

机构信息

Centre of Microbial and Plant Genetics, Department of Microbial and Molecular Systems (M²S), KU Leuven, Leuven, Belgium.

Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium.

出版信息

Allergy. 2019 Jan;74(1):100-110. doi: 10.1111/all.13502. Epub 2018 Oct 8.

DOI:10.1111/all.13502
PMID:29888398
Abstract

BACKGROUND

There is an increasing interest in targeted application of probiotic bacteria for prevention and treatment of airway diseases, including allergies. Here, we investigated the beneficial effects of preventive intranasal treatment with probiotics Lactobacillus rhamnosus GG and L. rhamnosus GR-1 in a mouse model of allergic asthma.

METHODS

Lactobacillus rhamnosus was administered intranasally eight times on days 1-4 and 8-11 at 5 × 10  CFU/dose, followed by a 2-week asthma induction protocol with birch pollen extract on alternating days. Effects of preventive treatment were analyzed based on serum antibody levels, bronchoalveolar lavage cell counts, lung histology, lung cytokine levels, and airway hyperreactivity. Colonization and translocation of L. rhamnosus were assessed by bacterial cell counts in nasal mucosa, fecal samples, cervical lymph nodes, and blood. Binding of fluorescent L. rhamnosus to fixed murine nasal mucosal cells and airway macrophages was visualized by fluorescence microscopy.

RESULTS

Transient colonization of the murine upper airways by L. rhamnosus GG was demonstrated and was approximately ten times higher compared to L. rhamnosus GR-1. Marked binding of fluorescent L. rhamnosus GG to murine nasal mucosal cells and airway macrophages was visualized. Preventive treatment with L. rhamnosus GG (but not L. rhamnosus GR-1) resulted in a significant decrease in bronchoalveolar lavage eosinophil counts, lung interleukin-13 and interleukin-5 levels, and airway hyperreactivity. A tendency toward a decrease in serum Bet v 1-specific immunoglobulin G1 was likewise observed.

CONCLUSION

Intranasally administered L. rhamnosus GG prevents the development of cardinal features of birch pollen-induced allergic asthma in a strain-specific manner.

摘要

背景

人们对靶向应用益生菌预防和治疗气道疾病(包括过敏)的兴趣日益增加。在这里,我们研究了鼠李糖乳杆菌 GG 和 L. rhamnosus GR-1 预防性鼻腔给药在变应性哮喘小鼠模型中的有益作用。

方法

在第 1-4 天和第 8-11 天,每天给予 5×10 个 CFU/剂量的鼠李糖乳杆菌 8 次,然后用桦树花粉提取物进行为期 2 周的哮喘诱导方案,隔一天进行一次。根据血清抗体水平、支气管肺泡灌洗液细胞计数、肺组织学、肺细胞因子水平和气道高反应性分析预防性治疗的效果。通过鼻黏膜、粪便样本、颈淋巴结和血液中的细菌细胞计数评估 L. rhamnosus 的定植和易位。通过荧光显微镜观察固定的鼠鼻黏膜细胞和气道巨噬细胞上荧光标记的 L. rhamnosus 的结合情况。

结果

证明了 L. rhamnosus GG 对鼠上呼吸道的短暂定植,并且比 L. rhamnosus GR-1 高约 10 倍。观察到荧光 L. rhamnosus GG 与鼠鼻黏膜细胞和气道巨噬细胞的明显结合。预防性给予 L. rhamnosus GG(而不是 L. rhamnosus GR-1)可显著减少支气管肺泡灌洗液嗜酸性粒细胞计数、肺白细胞介素-13 和白细胞介素-5 水平以及气道高反应性。同样观察到血清 Bet v 1 特异性免疫球蛋白 G1 有下降的趋势。

结论

经鼻腔给予 L. rhamnosus GG 以菌株特异性方式预防桦树花粉诱导的变应性哮喘的主要特征的发展。

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