Feleszko W, Jaworska J, Rha R-D, Steinhausen S, Avagyan A, Jaudszus A, Ahrens B, Groneberg D A, Wahn U, Hamelmann E
Department of Pediatric Pneumology and Allergy, The Medical University Children's Hospital, Warszawa, Poland.
Clin Exp Allergy. 2007 Apr;37(4):498-505. doi: 10.1111/j.1365-2222.2006.02629.x.
Microbial intestinal colonization in early in life is regarded to play a major role for the maturation of the immune system. Application of non-pathogenic probiotic bacteria during early infancy might protect from allergic disorders but underlying mechanisms have not been analysed so far.
The aim of the current study was to investigate the immune effects of oral application of probiotic bacteria on allergen-induced sensitization and development of airway inflammation and airway hyper-reactivity, cardinal features of bronchial asthma.
Newborn Balb/c mice received orally 10(9) CFU every second day either Lactobacillus rhamnosus GG or Bifidobacterium lactis (Bb-12) starting from birth for consecutive 8 weeks, during systemic sensitization (six intraperitoneal injections, days 29-40) and airway challenge (days 54-56) with ovalbumin.
The administration of either Bb-12 or LGG suppressed all aspects of the asthmatic phenotype: airway reactivity, antigen-specific immunoglobulin E production and pulmonary eosinophilia (mean: 137 vs. 17 and 13 cellsx10(3)/mL, respectively). Antigen-specific recall proliferation by spleen cells and T-helper type 2 cytokine production (IL-4, IL-5 and IL-10) by mesenteric lymph node cells also showed significant reduction, while TGF production remained unchanged. Oral LGG administration particularly suppressed allergen-induced proliferative responses and was associated with an increase in numbers of TGF-beta-secreting CD4+/CD3+ T cells in mesenteric lymph nodes (6.5, 16.7%) as well as nearly 2-fold up-regulation of Foxp3-expressing cells in peribronchial lymph nodes.
Neonatal application of probiotic bacteria inhibits subsequent allergic sensitization and airway disease in a murine model of asthma by induction of T regulatory cells associated with increased TGF-beta production.
生命早期微生物在肠道的定植被认为对免疫系统的成熟起着重要作用。婴儿早期应用非致病性益生菌可能预防过敏性疾病，但目前尚未分析其潜在机制。
本研究旨在探讨口服益生菌对变应原诱导的致敏作用以及气道炎症和气道高反应性（支气管哮喘的主要特征）发展的免疫影响。
新生Balb/c小鼠从出生开始每隔一天口服10⁹CFU鼠李糖乳杆菌GG或乳酸双歧杆菌（Bb-12），连续8周，在此期间进行全身致敏（第29 - 40天腹腔注射6次）和用卵清蛋白进行气道激发（第54 - 56天）。
Bb-12或LGG的给药均抑制了哮喘表型的各个方面：气道反应性、抗原特异性免疫球蛋白E产生和肺部嗜酸性粒细胞增多（平均值分别为137对17和13个细胞×10³/mL）。脾细胞的抗原特异性回忆增殖以及肠系膜淋巴结细胞产生的2型辅助性T细胞细胞因子（IL-4、IL-5和IL-10）也显著降低，而转化生长因子的产生保持不变。口服LGG尤其抑制了变应原诱导的增殖反应，并与肠系膜淋巴结中分泌转化生长因子-β的CD4⁺/CD3⁺T细胞数量增加（6.5%，16.7%）以及支气管周围淋巴结中表达Foxp3的细胞上调近2倍有关。
在哮喘小鼠模型中，新生儿期应用益生菌通过诱导与转化生长因子-β产生增加相关的调节性T细胞，抑制随后的过敏性致敏和气道疾病。
