Impact of Maternal Antibiotics on the Breastfeeding Infant Microbiome and Metabolome

项目摘要 这个数据科学项目提案旨在利用创新方法， 代谢组学和微生物组学分析，以研究母体抗生素暴露对 母乳喂养婴儿。当母乳喂养的母亲服用抗生素治疗常见感染时， 婴儿的微生物组及其代谢可能会受到影响。这可能是长期的 对婴儿的整体健康的后果，因为微生物组的重要作用， 健康和疾病。由于婴儿的低血糖水平， 血容量和抽血的侵入性。我们已经能够非侵入性地 使用皮肤拭子监测皮肤中的药物。我们认为这可能是一种重要的新的监测方式 婴儿的药物。该项目将调查的三个领域是： 目的1：通过监测母乳中的抗生素水平， 使用非侵入性拭子进行皮肤代谢组学研究。我们将测试母乳喂养婴儿的皮肤 母亲被给予抗生素，母乳喂养的婴儿，母亲没有被给予抗生素， 抗生素，以及那些没有母乳喂养的婴儿，他们的母亲被给予抗生素， 项目1。非靶向代谢组学和分子网络将用于检测抗生素 及其代谢物的作用。 目的2：确定通过母乳接触抗生素对婴儿的影响 微生物组、代谢组和代谢转化能力。 将分析从项目1中获得的婴儿粪便样本，以确定微生物组的变化 从母亲那里得到抗生素我们将比较四种不同的抗生素在 临床研究影响婴儿的微生物组和代谢组。 目的3：阐明幼鼠肠道代谢的直接或间接转化 (via母亲治疗或母乳喂养）暴露于氨苄青霉素，并调查宿主 细胞色素P450（CYP450）活性改变。从项目2获得的小鼠样本将 使用新的数据科学应用程序进行分析，以确定氨苄青霉素的效果， 母乳对婴儿的整个肠道和肝脏的代谢，包括 细胞色素P450药物代谢酶（Cyp）。我们还将有针对性地分析 母乳中的氨苄青霉素来自我们的药物计量学和分析化学核心， 来自Milk Analytics Core的母乳分析，以补充我们的非针对性方法。 我们还将评估氨苄青霉素对小鼠肠和肝脏中Cyp活性的影响。

PROJECT SUMMARY This data science project proposal seeks to utilize innovative methods in untargeted metabolomics and microbiome analysis to study the effect of maternal antibiotic exposure in breastfeeding infants. When breastfeeding mothers are taking antibiotics for common infections, the infant's microbiome and their metabolism may be affected. This could have long-term consequences on the infant's overall health because of the important role of the microbiome in health and disease. It can be difficult to monitor drug effects in infants because of their low blood volume and the invasiveness of blood draws. We have been able to non-invasively monitor drugs in skin using skin swabs. We think this may be an important new way to monitor drugs in infants. The three areas to be investigated in this project are: Aim 1: Monitor infant antibiotic exposure levels through breast milk by monitoring the skin metabolome using non-invasive swabs. We will test skin from breast milk fed infants whose mothers were given antibiotics, breast milk fed infants whose mothers were not given antibiotics, and infants who are not breast fed whose mothers were given antibiotics from Project 1. Untargeted metabolomics and molecular networking will be used to detect antibiotics and their metabolites in skin. Aim 2: Determine the impact of antibiotic exposure through breast milk on the infant microbiome, metabolome and metabolic transformation capacity. Infant fecal samples obtained from Project 1 will be analyzed for changes in the microbiome due to antibiotics from the mother. We will compare how the four different antibiotics given in the clinical study affect the infant microbiome and metabolome. Aim 3: Elucidate the gut metabolic transformations in infant mice from direct or indirect (via maternal treatment or breastfeeding) exposure to ampicillin and investigate if host cytochrome P450 (CYP) activities are altered. Mouse samples obtained from Project 2 will be analyzed using new data science applications to determine the effect of ampicillin through breast milk on the infant's metabolism throughout the intestine and the liver including the cytochrome P450 drug metabolizing enzymes (Cyp). We will also have the targeted analysis of ampicillin in breast milk from our Pharmacometrics and Analytical Chemistry Core and the breast milk analysis from the Milk Analytics Core to complement our untargeted approaches. We will also assess the effect of ampicillin on Cyp activity in the mouse intestine and liver.