The Effect of Dog-Keeping and the Intestinal Microbiota on Immune Development

早期接触宠物与降低过敏性疾病的风险有关。然而，这种关联的机制尚不清楚。这项研究的目的是确定养狗如何影响早期免疫发育，以及这种保护是否与婴儿肠道的细菌特征有关。我们的假设是养狗改变了细菌群落的组成 (BCC)在家里，并反过来影响婴儿肠道细菌含量（微生物群）的建立。此外，养狗，最有可能通过改变肠道微生物群，以某种方式影响儿童早期免疫发育，这解释了观察到的较低的过敏风险。我们的目标是： 1)为了比较生活在有狗的家庭中的儿童与生活在无宠物家庭中的儿童在生命的前18个月期间的免疫发育的标志物，2）为了比较生活在有狗的家庭中的婴儿与生活在无宠物家庭中的婴儿之间的肠道BCC的特征，如通过在6个月大时收集的粪便样品所反映的，和3）将肠道微生物群的特征与生命最初18个月内免疫发育的标志物相关联。方法：新生儿队列 在怀孕期间招募母亲后，将对出生于有狗（n=60）和无宠物家庭（n=60）的婴儿进行评价。将使用出生时、6个月和18个月的数据点，分析和比较来自养狗家庭与无宠物家庭的儿童的相关健康结局和免疫发育纵向轨迹模式的调查数据。免疫结局将包括总IgE水平、树突状细胞和调节性T细胞上的发育和成熟标志物以及细胞因子分泌谱 对有丝分裂原、先天刺激和IgE交联抗体反应。在18个月时，还将评价对尘螨和破伤风抗原的免疫应答以及对常见过敏原的特异性IgE水平。肠道微生物群将通过使用PhyloChip对6个月龄时的粪便样本进行非培养分析来表征。肠道细菌特性将比较狗暴露的婴儿之间 以及那些来自无宠物家庭的人，并分析其与健康结果和免疫发育模式的相关性。

Early life pet exposure has been associated with lowered risk of allergic disorders. However, the mechanism underlying this association is unknown. The objective of this research is to determine how dog-keeping impacts early life immune development and whether this protection is associated with the bacterial profile of an infant's intestinal tract. Our hypothesis is that dog-keeping alters the bacterial community composition (BCC) in the home and, in turn, impacts the establishment of an infant's intestinal bacterial content (microbiota). Furthermore, dog-keeping, most likely through altering the intesfinal microbiota, affects early childhood immune development in a manner that explains the observed lower risk of allergy. Our aims are: 1) To compare markers of immune development during the first 18 months of life among children living in homes that contain a dog versus those living in pet-free homes, 2) To compare characteristics of the intestinal BCC, as reflected by stool samples collected at 6 months of age, between infants living in homes that contain a dog versus those living in pet-free homes, and 3) To correlate characteristics of the intestinal microbiota to markers of immune development over the first 18 months of life. Methods: A cohort of neonates born into dog-containing (n=60) and pet-free homes (n=60) will be evaluated following maternal recruitment during pregnancy. Survey data on relevant health outcomes and longitudinal trajectory patterns of immune development will be analyzed and compared in the children from dog-containing versus pet-free homes using datapoints at birth, 6 and 18 months of life. Immune outcomes will include total IgE level, developmental and maturation markers on dendritic cells and regulatory T cells and cytokine secretion profile in response to mitogen, innate stimuli and IgE cross-linking antibody. At 18 months, immune responses to dust mite and tetanus antigen and specific IgE levels to common allergens will also be evaluated. The intestinal microbiota will be characterized by culture-independent analyses of stool samples at 6 months of age using the PhyloChip. Intestinal bacterial characteristics will be compared between dog-exposed infants and those from pet-free homes and analyzed for correlation to health outcomes and patterns of immune development.