Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering, University of Antwerp , Antwerp, Belgium.
Centre of Microbial and Plant Genetics, Department of Microbial and Molecular Systems (M2S), KU Leuven , Leuven, Belgium.
Gut Microbes. 2020 Nov 1;11(6):1729-1744. doi: 10.1080/19490976.2020.1766345. Epub 2020 Jun 10.
Allergic asthma is a highly prevalent inflammatory disease of the lower airways, clinically characterized by airway hyperreactivity and deterioration of airway function. Immunomodulatory probiotic bacteria are increasingly being explored to prevent asthma development, alone or in combination with other treatments. In this study, wild-type and recombinant probiotic GR-1 were tested as preventive treatment of experimental allergic asthma in mice. Recombinant GR-1 was designed to produce the major birch pollen allergen Bet v 1, to promote allergen-specific immunomodulation. Administration of wild-type and recombinant GR-1 prevented the development of airway hyperreactivity. Recombinant GR-1 also prevented elevation of airway total cell counts, lymphocyte counts and lung IL-1β levels, while wild-type GR-1 inhibited airway eosinophilia. Of note, a shift in gut microbiome composition was observed after asthma development, which correlated with the severity of airway inflammation and airway hyperreactivity. In the groups that received GR-1, this asthma-associated shift in gut microbiome composition was not observed, indicating microbiome-modulating effects of this probiotic. These data demonstrate that GR-1 can prevent airway function deterioration in allergic asthma. Bet v 1 expression by GR-1 further contributed to lower airway inflammation, although not solely through the expected reduction in T helper 2-associated responses, suggesting involvement of additional mechanisms. The beneficial effects of GR-1 correlate with increased gut microbiome resilience, which in turn is linked to protection of airway function, and thus further adds support to the existence of a gut-lung axis.
过敏性哮喘是一种常见的下呼吸道炎症性疾病,临床上表现为气道高反应性和气道功能恶化。免疫调节益生菌越来越多地被探索用于预防哮喘的发生,单独使用或与其他治疗方法联合使用。在这项研究中,野生型和重组益生菌 GR-1 被测试作为预防实验性变应性哮喘的治疗方法。重组 GR-1 被设计用来产生主要的桦树花粉过敏原 Bet v 1,以促进过敏原特异性免疫调节。野生型和重组 GR-1 的给药可预防气道高反应性的发展。重组 GR-1 还可预防气道总细胞计数、淋巴细胞计数和肺 IL-1β 水平的升高,而野生型 GR-1 抑制气道嗜酸性粒细胞增多。值得注意的是,在哮喘发展后观察到肠道微生物组组成的变化,这与气道炎症和气道高反应性的严重程度相关。在接受 GR-1 的组中,这种与哮喘相关的肠道微生物组组成的变化没有观察到,这表明这种益生菌具有调节微生物组的作用。这些数据表明,GR-1 可预防变应性哮喘的气道功能恶化。GR-1 表达的 Bet v 1 进一步导致下气道炎症,尽管不是完全通过预期的减少辅助性 T 细胞 2 相关反应,这表明涉及其他机制。GR-1 的有益效果与增加肠道微生物组的弹性相关,这反过来又与气道功能的保护有关,因此进一步支持了肠道-肺部轴的存在。
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