Yoo Jennifer, Tcheurekdjian Haig, Lynch Susan V, Cabana Michael, Boushey Homer A
Division of Allergy and Immunology, Department of Medcine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0130, USA.
Proc Am Thorac Soc. 2007 Jul;4(3):277-82. doi: 10.1513/pats.200702-033AW.
The "hygiene hypothesis" proposes that the increase in allergic diseases in developing countries reflects a decrease in infections during childhood. Cohort studies suggest, however, that the risks of asthma are increased in children who suffer severe illness from a viral respiratory infection in infancy. This apparent inconsistency can be reconciled through consideration of epidemiologic, clinical, and animal studies. The elements of this line of reasoning are that viral infections can predispose to organ-specific expression of allergic sensitization, and that the severity of illness is shaped by the maturity of immune function, which in turn is influenced by previous contact with bacteria and viruses, whether pathogenic or not. Clinical studies of children and interventional studies of animals indeed suggest that the exposure to microbes through the gastrointestinal tract powerfully shapes immune function. Intestinal microbiota differ in infants who later develop allergic diseases, and feeding Lactobacillus casei to infants at risk has been shown to reduce their rate of developing eczema. This has prompted studies of feeding probiotics as a primary prevention strategy for asthma. We propose that the efficacy of this approach depends on its success in inducing maturation of immune function important in defense against viral infection, rather than on its effectiveness in preventing allergic sensitization. It follows that the endpoints of studies of feeding probiotics to infants at risk for asthma should include not simply tests of responsiveness to allergens, but also assessment of intestinal flora, immune function, and the clinical response to respiratory viral infection.
“卫生假说”提出，发展中国家过敏性疾病的增加反映出儿童期感染的减少。然而，队列研究表明，婴儿期因病毒性呼吸道感染而患重病的儿童患哮喘的风险会增加。通过对流行病学、临床和动物研究的考量，这种明显的矛盾可以得到调和。这一推理思路的要点在于，病毒感染可促使过敏性致敏的器官特异性表达，而疾病的严重程度取决于免疫功能的成熟度，免疫功能又反过来受先前接触细菌和病毒（无论是否致病）的影响。对儿童的临床研究和对动物的干预研究确实表明，通过胃肠道接触微生物会有力地塑造免疫功能。后来患过敏性疾病的婴儿其肠道微生物群有所不同，并且已证明给有风险的婴儿喂食干酪乳杆菌可降低他们患湿疹的几率。这促使人们研究将喂食益生菌作为哮喘的一级预防策略。我们认为，这种方法的疗效取决于其能否成功诱导对抵御病毒感染至关重要的免疫功能成熟，而非取决于其预防过敏性致敏的效果。因此，对有哮喘风险的婴儿喂食益生菌的研究终点不仅应包括对过敏原反应性的测试，还应包括对肠道菌群、免疫功能以及对呼吸道病毒感染的临床反应的评估。
