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

养狗和肠道微生物群对免疫发育的影响

• 批准号: 8567837
• 负责人: EDWARD M ZORATTI
• 金额: $ 26.79万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8567837
• 关键词: Adult; Affect; Affinity; Age; Age-Months; Allergens; Allergic; Animals; Antibodies; Antigens; Asthma; Biological Markers; Birth; Canis familiaris; Characteristics; Child; Childhood; Communities; Data; Dendritic Cells; Development; Disease; Ecology; Enrollment; Epidemiologic Studies; Exhibits; Exposure to; Extrinsic asthma; Feces; Half-Life; Health; Home environment; Hygiene; Hypersensitivity; IgE; IgE Receptors; Immune; Immune response; Immune system; Immunologic Markers; Immunologic Receptors; Incidence; Infant; Inhalant dose form; Instruction; Intestines; Lead; Life; Ligands; Link; Measurable; Mediating; Medical; Methods; Metric; Microbe; Mitogens; Newborn Infant; Outcome; Pattern; Peripheral Blood Mononuclear Cell; Pregnancy; Production; Regulatory T-Lymphocyte; Relative (related person); Reporting; Research; Risk; Sampling; Serum; Stimulus; Surveys; Taxon; Tetanus; base; cohort; crosslink; cytokine; design; early childhood; microbial; microbial community; microbiome; neonate; novel; pet animal; prevent; pyroglyphid; receptor; response; stem; theories

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.

生命早期接触宠物与降低过敏性疾病的风险有关。然而，这种关联背后的机制尚不清楚。这项研究的目的是确定养狗如何影响生命早期的免疫发育，以及这种保护是否与婴儿肠道的细菌状况有关。我们的假设是养狗改变了细菌群落的组成 （BCC）在家中，进而影响婴儿肠道细菌含量（微生物群）的建立。此外，养狗很可能通过改变肠内微生物群来影响儿童早期的免疫发育，从而解释了观察到的过敏风险较低的情况。我们的目标是： 1) 比较生活在有狗的家庭中的儿童与生活在没有宠物的家庭中的儿童在生命的前 18 个月内的免疫发育标志物，2) 比较肠道 BCC 的特征，如在6 个月大时，生活在有狗的家庭中的婴儿与生活在没有宠物的家庭中的婴儿之间的比较，以及 3) 将肠道微生物群的特征与生命前 18 个月内的免疫发育标志物相关联。方法：一组新生儿 出生在有狗的家庭（n = 60）和无宠物的家庭（n = 60）将在怀孕期间招募母亲后进行评估。将使用出生时、6 个月和 18 个月的数据点，对来自有狗家庭和无宠物家庭的儿童的相关健康结果和免疫发展纵向轨迹模式的调查数据进行分析和比较。免疫结果将包括总 IgE 水平、树突状细胞和调节性 T 细胞的发育和成熟标记物以及细胞因子分泌谱 响应有丝分裂原、先天刺激和 IgE 交联抗体。 18 个月时，还将评估对尘螨和破伤风抗原的免疫反应以及对常见过敏原的特异性 IgE 水平。将使用 PhyloChip 对 6 个月大的粪便样本进行独立于培养的分析来表征肠道微生物群。将比较暴露于狗的婴儿之间的肠道细菌特征 以及来自无宠物家庭的那些，并分析其与健康结果和免疫发育模式的相关性。