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Developmental CSE: Impact on Intestinal Bacterial Community Development

发育性 CSE：对肠道细菌群落发育的影响

基本信息

批准号：
9377764
负责人：
Rachel Elizabeth Neal
金额：
$ 45.5万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9377764
关键词：
Adult Age Animal Husbandry Animal Model Archives Bacteria Bile Acids Birth Breathing Butyrates Carbohydrates Child Cigarette Classification Coenzyme A-Transferases Communities Community Developments Consumption Cotinine DNA Data Set Development Exposure to Fatty Acids Fermentation Formate-Tetrahydrofolate Ligase Gene Expression Growth Hour Human Human Microbiome Impairment Individual Infant Inhalation Exposure Intestines Isotope Labeling Label Laboratories Libraries Life Low Birth Weight Infant Maintenance Measures Metabolic Metabolism Modeling Mothers Mus Neonatal Newborn Infant Outcome Pathogenicity Phenotype Population Pregnancy Preparation Production RNA Resistance Role Sampling Smoke Smoking Stable Isotope Labeling Starch Statistical Data Interpretation Structure Supervision Testing Tissue Banks Tobacco Tobacco smoke Toxin Training Very Low Birth Weight Infant Volatile Fatty Acids Weight World Health Organization analog carbohydrate metabolism cigarette smoking environmental tobacco smoke exposure graduate student gut microbiome maternal cigarette smoking metabolome metabolomics microbial community microbiome mouse model offspring postnatal prenatal tributyrin undergraduate student

项目摘要

ABSTRACT: Cigarette smoke is one of the most prevalent developmental toxins. The World Health Organization estimates that ~700 million children worldwide are exposed either pre- and/or postnatally to cigarette smoke. The overarching theme of this proposal is to study the role of developmental cigarette smoke exposure on the colonization, maintenance, and function of the gut microbiome. Since neonatal gut colonization is initiated by exposure to maternal bacteria during birth, and tobacco smoke exposure alters cecal bacterial content in adults, we propose that maternal tobacco smoke exposure during pregnancy results in aberrant bacterial colonization of the neonatal gut such that pathogenic bacterial overgrowth occurs, and that continued cigarette smoke exposure during postnatal development entrenches this phenotype. Utilizing a unique and well characterized murine inhalation model simulating maternal cigarette smoking during pregnancy, and newborn smoke exposure - established in our laboratory - we will: 1) Examine the impact of developmental cigarette smoke exposure on offspring gut microbial community colonization and the persistence of the microbiome phenotype; 2) Examine the impact of developmental cigarette smoke exposure on offspring gut microbial community function; and 3) Compare the outcomes within our murine model of developmental tobacco cigarette smoke exposure with findings from very low birth weight human infants of mothers who smoked during pregnancy. Central Hypothesis: Developmental cigarette smoke exposure induces pathogenic intestinal bacterial colonization with persistent alterations in carbohydrate metabolism in mice, with a similar impact in very low birth weight infants of mothers who smoked during pregnancy.

摘要：香烟烟雾是最普遍的发育毒素之一。世界卫生组织估计全世界约有7亿儿童在出生前和/或出生后暴露于香烟烟雾。的这项建议的首要主题是研究发育中的香烟烟雾暴露对肠道微生物组的定殖、维持和功能。由于新生儿肠道定植是由出生时暴露于母体细菌和烟草烟雾暴露会改变盲肠细菌含量，对于成年人，我们认为母亲在怀孕期间接触烟草烟雾会导致异常的细菌感染，新生儿肠道的定植，使得病原性细菌过度生长发生，并且持续的香烟出生后发育期间的烟雾暴露巩固了这种表型。利用一个独特的，特征性小鼠吸入模型，模拟妊娠期间母亲吸烟，吸烟暴露-在我们的实验室建立-我们将：1）检查发展香烟的影响烟雾暴露对后代肠道微生物群落定植和微生物组持久性的影响表型; 2）检查发育中的香烟烟雾暴露对后代肠道微生物的影响社区功能;以及3）比较我们的发育烟草小鼠模型中的结果吸烟母亲的极低出生体重婴儿的吸烟暴露孕期中心假设：发育中的香烟烟雾暴露诱导致病性小鼠肠道细菌定植，碳水化合物代谢持续改变，在怀孕期间吸烟的母亲的极低出生体重婴儿中也有类似的影响。