基于肠道免疫屏障的生命早期环境抗生素暴露对儿童过敏性疾病的影响及机制研究

The current situation of antibiotics abuse is staggering in China, especially veterinary antibiotics which were forbidden in infants and toddlers. Only one cross sectional study on internal exposure. It’s more challenging to investigate the chronic biological health effects of persistent low concentration veterinary antibiotic exposure in early life. A random sample of 49.8% of Shanghai eugenic birth cohort had positive urine environmental antibiotics in the second trimester and increased the incidence of allergic diseases in their children. This study will first determine the level of environmental antibiotic exposure in the early life, and based on a large prospective birth cohort，we further determine the association between pregnancy and infant antibiotic exposure and childhood allergic diseases as well association strength. Pre-experimental studies have found that that low concentration tetracycline, a characteristic contaminant, affected zebrafish intestinal goblet cells numbers and inflammatory factors expression in, and proposed the hypothesis that environmental antibiotics may effects offspring's intestinal immune developmental toxicity. Using established zebrafish poisoning models, inflammatory responses and atopy responses are used as effect markers to explore the role of environmental antibiotics in the immunotoxicity of the intestinal mucosal barrier caused by the interaction of intestinal flora and goblet cells. This research will benefit for humans to raise the awareness of environmental health effects of antibiotics, it is very helpful in controlling antibiotic abuse, improving the population quality and making related government policies.

我国抗生素滥用形势严峻，以儿童禁用的兽类抗生素为著。目前仅有一项环境抗生素横断面内暴露的调查，生命早期低浓度慢性兽类抗生素暴露的远期生物健康效应信息几近空白。我们随机抽样发现49.8%的上海优生儿童队列的孕中期母亲尿液环境抗生素阳性，且其子女过敏性疾病发病率增高。本研究将首先明确生命早期的环境抗生素内暴露水平，在大型前瞻性出生队列的基础上进一步明确孕期与婴幼儿期抗生素和儿童过敏性疾病的关联及关联强度。在前期预实验发现低浓度的特征性污染物四环素影响了斑马鱼肠道杯状细胞数目和炎症因子的基础上，提出环境抗生素可能影响子代肠道免疫发育毒性的假说，利用已建成的斑马鱼染毒模型，以炎症反应与特应性反应为效应标志物，探索环境抗生素对肠道菌群与杯状细胞共同作用所致的肠道黏膜屏障的免疫毒性的作用。本研究有利于人类提高环境抗生素健康效应的认知，对控制抗生素滥用、提高人口素质和国家政策制订具有重大的指导意义。

我国抗生素滥用形势严峻，以儿童禁用的兽类抗生素为著。目前仅有一项环境抗生素横断面内暴露的调查，生命早期低浓度慢性兽类抗生素暴露的远期生物健康效应信息几近空白。我们随机抽样发现49.8%的上海优生儿童队列的孕中期母亲尿液环境抗生素阳性，且其子女过敏性疾病发病率增高。本研究将首先明确生命早期的环境抗生素内暴露水平，在大型前瞻性出生队列的基础上进一步明确孕期与婴幼儿期抗生素和儿童过敏性疾病的关联及关联强度。本课题在前期预实验发现低浓度的特征性污染物四环素影响了斑马鱼肠道杯状细胞数目和炎症因子的基础上，完成了环境抗生素可能影响子代肠道免疫发育毒性研究，利用已建成的斑马鱼染毒模型，以炎症反应与特应性反应为效应标志物，完成了环境抗生素对肠道菌群与杯状细胞共同作用所致的肠道黏膜屏障的免疫毒性的作用。本研究共发表文章14篇，极其相关9篇。