Research Progress of Probiotics in Improving Milk Protein Allergy
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摘要: 牛奶蛋白过敏是儿童早期最常见的食物过敏反应之一，通常会持续到成年期。益生菌影响肠道微生物群并调节免疫反应。因此，它可能是可以缓解某些涉及肠道免疫系统疾病的工具，例如尚无治疗方法的牛乳蛋白过敏。本文中探讨了牛奶蛋白过敏的重要研究进展，介绍了牛乳蛋白过敏原和过敏机理。重点强调了益生菌在牛奶蛋白过敏方面取得的最新进展，通过调节肠道菌群和提高肠道免疫来改善牛乳蛋白过敏。最后阐述了低致敏性产品的研究现状，提出了研究及应用中面临的主要问题。益生菌改善牛乳蛋白过敏性的深入研究是过敏领域的重大突破，为缓解牛乳过敏提供理论依据。Abstract: Cow milk protein allergy is one of the most common food allergic reactions in early childhood and often persists through adult life. Probiotics have influence on the intestinal microbiota and modulate the immune response. They may be tools that prevent or alleviate certain pathologies involving the gut immune system, such as cow milk protein allergy. In this review, significant research advances on cow milk protein allergy are explored, milk protein allergens and allergy mechanism are introduced. This review highlights recent progress in the probiotics related tothe cow milk protein allergy, which could improve milk protein allergy by regulating intestinal flora and improving intestinal immunity. Finally, the research status of hypoallergenic products is described as well as the problems faced in research and application are put forward. The in-depth study of probiotics to improve milk protein allergy has been a major breakthrough in the field of allergies, providing the theoretical basis for alleviating milk allergy.
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Key words:
- probiotics /
- milk protein /
- immune function /
- intestinal flora /
- allergy /
- mechanism /
- hypoallergenic products
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蛋白种类 致敏原 Uniprot 等电点 浓度（g/L） 占总蛋白的比例（%） 分子量（kDa） 氨基酸数量 生物功能 αs1-酪蛋白 Bos d9 P02662 4.9~5 12~15 29 23.6 199 钙结合蛋白 αs2-酪蛋白 Bos d10 P02663 5.2~5.4 3~4 8 25.2 207 钙结合蛋白 β-酪蛋白 Bos d11 P02666 5.1~5.4 9~11 27 24.0 209 钙结合蛋白 κ-酪蛋白 Bos d12 P02668 5.4~5.6 3~4 10 19.0 169 钙的稳定和凝固 β-乳球蛋白 Bos d5 P02754 5.3 3~4 10 18.3 162 脂质结合蛋白 α-乳白蛋白 Bos d4 P00711 4.8 1~1.5 5 14.2 123 参与乳糖的合成；结合脂质、矿物质 免疫球蛋白 Bos d6 − − 0.6~1.0 3 150.0 − 防御病毒 牛血清蛋白 Bos d7 P02769 4.9~5.1 0.1~0.4 1 66.3 582 配体的运输，保护自由基 
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表 2 牛乳蛋白诱导机制的区别
Table 2. Differences in milk protein induction mechanism
项目 IgE介导 非IgE介导 患病率 高 低 年龄 婴幼儿 婴幼儿和成人 机制 免疫学
-IgE免疫学
-细胞介导
-复合免疫症状 一种或多种胃肠道、皮肤、呼吸道、过敏反应 主要是胃肠道和/或呼吸道疾病 摄入后的发病时间 小于1 h 大于1 h至数天 预防 母乳喂养
婴儿避免摄入牛乳蛋白（0~6个月）避免食用牛乳蛋白 处理 去除过敏原表位-牛乳蛋白水解 去除过敏原表位
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表 3 益生菌对牛乳过敏的改善作用
Table 3. Improvement effect of probiotics on milk allergy
改善作用 益生菌 改善原因 参考文献 调节肠道菌群 鼠李糖乳杆菌LA305，唾液乳杆菌LA307和长双歧杆菌婴儿亚种LA308 平衡肠道菌群的丰度及结构，影响免疫调节和耐受 [17] 促进sIgA增加，增强肠粘膜屏障功能 鼠李糖乳杆菌GG 增强B细胞的活化，显著提高小鼠肠道黏膜sIgA的分泌量，调节黏膜免疫系统 [18] 短双歧杆菌M-16V 增强了小鼠肠道内IgA的合成，促进了早期黏膜免疫的发展 [19] 嗜酸乳杆菌和乳双歧杆菌 增加肠黏膜sIgA含量，增强小鼠特异性及非特异性免疫功能 [20] 减少Th2极化，保持Th1/Th2平衡 植物乳杆菌ZDY2013和鼠李糖乳杆菌GG 诱导Th1或调节性T细胞分化抑制Th2的反应；显著增加了紧密连接蛋白的相对表达，增强肠道屏障功能 [21] 嗜酸乳杆菌和双歧杆菌 使血清中Th2特异性免疫应答向Th1倾斜，抑制了血清中IgE的产生，从而减轻小鼠对乳清蛋白的过敏反应 [22] 诱导Foxp3+Treg，保持Treg/Th17的平衡 副干酪乳杆菌L9或长双歧杆菌BBMN68 刺激树突细胞（如CD11c+CD103+ DCs）的表达和诱导T细胞转换Foxp3+Treg [23-24]
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菌名 菌群丰度增加 菌群丰度降低 鼠李糖乳杆菌LA305 消化球菌科（Peptococcaceae）、瘤胃球菌科（Ruminococcaceae）、
Odoribacter梭菌属（Clostridium sensu stricto）、Marvinbryantia 唾液乳杆菌LA307 普雷沃氏菌科（Prevotellaceae）NK3B31、Odoribacter Marvinbryantia 长双歧杆菌婴儿亚种LA308 毛螺旋菌科（Lachnospiraceae）NK4A136 厌氧原体菌属（Anaeroplasma）、Marvinbryantia
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