Prenatal Cigarette Smoke Exposure: Impact on Offspring Gut Bacterial Microbiome

摘要 据估计，肯塔基州有17%的女性在怀孕期间吸烟。在这次更新中提出的研究 应用程序使用发育良好的暴露于烟草烟雾的小鼠模型。我们已经展示了 出生前吸烟暴露(CSE)对新生儿体重、追赶生长和肠道细菌的影响 小鼠母鼠及其后代中的微生物群，以及对后代表型的影响(初步数据)。 然而，我们不知道观察到的微生物组的变化与后代表型是否有联系。我们会 测量盲肠微生物群或饮食抗性淀粉的转移对这些措施的影响 模特。 我们的中心假设是，CSE诱导的肠道微生物群变化与后代表型有关，这将是 在两个目标内进行测试： 目的1：利用断奶仔猪盲肠移植分离CSE诱导的微生物群和CSE本身 目的2：在青春期前和青春期后使用抗膳食淀粉增加短链脂肪酸 如果我们的中心假设得到支持，未来的研究将深入研究肠道-肝脏-脑轴的后果 以及调查潜在的干预措施。 Corbitt博士(Pi)、Neal博士(co-I)和Kosiewicz博士(co-I)将共同培训学生并进行拟议的研究。

ABSTRACT An estimated 17% of women in Kentucky smoke during pregnancy. The studies proposed within this renewal application use a well-developed murine model of developmental exposure to tobacco smoke. We have shown effects of prenatal cigarette smoke exposure (CSE) on birth weight, catch-up growth, and gut bacterial microbiome in mouse dams and their offspring, as well as effects on offspring phenotype (preliminary data). However, we do not know if the observed changed in microbiome and offspring phenotype are linked. We will measure the effect of cecal transfer of microbiomes or dietary resistant starch on those same measures in this model. Our central hypothesis, that CSE-induced gut microbiome alterations are linked to offspring phenotype, will be tested within 2 aims: Aim 1: use cecal transfer in weanlings to separate effects of CSE-induced microbiome from CSE itself Aim 2: use dietary resistant starch to increase short-chain fatty acids before vs after puberty If our central hypothesis is supported, future studies will delve into gut-liver-brain axis consequences of intestinal dysbiosis, as well as investigate potential interventions. Drs. Corbitt (PI), Neal (co-I), and Kosiewicz (co-I) jointly will train students and conduct the proposed studies.