婴儿期环境因素与儿童过敏性疾病关系研究

The infants born in Chengdu will be recruited for a cohort and nested case-control study. These infants will be investigated for the potent association of their delivery mode, living environment, feeding habits, medical treatment and other environmental factors from 0-1 year with the incedence of allergic disease (such as eczema, atopic dermatitis, asthma) during 0-2 years.The fecal samples of them during 0-1 year will be taxonomiocally analyzed with molecular methods.The differences will be characterized in the structure of fecal microbiota and predominate groups between allergic and healthy infants by which to explore the role of fecal microbiota in the etiology of allergic diseases. Animal studies will be conducted to confirm if caesarean, diet with high energy, high fat, high salt, antibiotics treatment would significantly implicate the sensitization of host animal to allergen attack, and know if and how fecal microbiota woule be involoved in allegic disease. Using cell line, test animal, we would like to evaluate the immune regulatory and anti-inflammatory effects of probiotics, the component and metabolites of probiotics, and find or/ document their possibilities in management of allergic disorders due to the changes of environment in infancy. The results from the present study could systematically and deeply find or / specialize the environmental factors / risk factors which might impact children's health, and help us to understand the possible relationship between environmental factors and children's health. The results from the present study would be helpful in finding effective and reliable way to protect infants from allergic disease.

对成都市新生儿进行队列和嵌套病例对照研究，探讨婴儿期（0-1岁）环境因素（分娩方式、喂养方式、抗生素使用、居住环境等）与0-2岁婴幼儿过敏性疾病发生的关系；使用分子生物学技术分析婴儿期间肠道菌相及重要菌群的变化、发现健康婴幼儿和过敏性疾病患儿在肠道菌相和重要菌群组成上的差异；分析肠道菌相和过敏性疾病的关系；采用动物实验，确认分娩方式（顺产/剖腹产）、喂养方式（母乳喂养/人工喂养）和抗生素使用对过敏性疾病的影响、探讨肠内细菌在环境因素相关过敏性疾病中的作用；用细胞及动物实验，研究益生菌、其菌体成分及其代谢产物的免疫调节及抗炎症作用，确认其在过敏性疾病防治中利用的可能性。本研究拟在探讨导致我国儿童过敏性疾病发生的环境因素，为儿童过敏性疾病的早期预防提供科学依据，并寻找早期控制过敏性疾病的有效措施。

探讨我国儿童过敏性疾病发生相关的环境因素，为儿童过敏性疾病的早期预防及治疗提供确切的科学依据和有效的措施，本研究对成都市新生儿进行了队列和嵌套病例对照研究，通过分析其婴儿期肠道菌相及重要菌群的变化，验证了肠道细菌在环境因素相关过敏性疾病中的作用；同时配套动物及细胞实验深入地探究了肠道细菌影响过敏性疾病的相关机理和益生菌在过敏性疾病防治中的可能性。. 在4000人的队列研究中，本研究发现双亲过敏疾病史、母亲孕期饮食因素、孕期居住环境因素、孕期感染、婴儿混合喂养、婴儿一月患感染性疾病等在一定条件下是婴幼儿过敏性疾病可能的危险因素，影响过敏疾病发生的婴儿期关键环境因素集中于孕期母亲和婴儿出生后的短时间内。通过对婴儿肠道菌相结构分析，发现受试婴儿肠道细菌的菌相形成的关键时期是在出生后0-1月之间，母亲孕期有可能是婴儿肠道菌相构建的关键時期之一，该关键时期比本研究预期的更早。与健康婴儿相比，过敏性疾病患儿在出生时肠道菌相即存在差异，从而使得0-1月期间肠道菌相构建过程不同。此差异可能是过敏性疾病患儿肠道菌相特征之一，推测母亲孕期和婴儿出生后的1个月以内为过敏性疾病防治的关键期。. 在动物实验中，利用抗生素或益生菌干预不同生命时期的小鼠，证明了肠道菌群和过敏性疾病间的密切关系，发现生命早期的肠道细菌异常是诱导各种成年期过敏性疾病发生的最重要因素之一；同时证明了利用益生菌在防治过敏性疾病中的可能性。. 在细胞实验中，发现人体肠内乳杆菌及双歧杆菌能特异影响机体的免疫反应；特别是婴儿肠道来源的双歧杆菌菌株能特异性地黏附上皮细胞、诱导上皮细胞特别的免疫应答反应，可能是儿童过敏性疾病的早期预防行之有效的措施。