Impact of Maternal Antibiotics on the Breastfeeding Infant Microbiome and Metabolome

母体抗生素对母乳喂养婴儿微生物组和代谢组的影响

• 批准号: 10309711
• 负责人: Shirley M Tsunoda
• 金额: $ 21.02万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10309711
• 关键词: Adult; Affect; Amoxicillin; Ampicillin; Analytical Chemistry; Antibiotics; Area; Asthma; Azithromycin; Basic Science; Blood; Blood Volume; Breast Feeding; Breastfed infant; Celiac Disease; Chronic; Clavulanate; Clinical; Clinical Research; Complement; Cytochrome P450; Data; Data Science; Development; Diabetes Mellitus; Disease; Drug Monitoring; Enzymes; Exposure to; Health; Hepatic; Home environment; Human; Human Milk; Hypersensitivity skin testing; Individual; Infant; Infection; Intake; Intestines; Life; Liver; Mass Spectrum Analysis; Mediating; Metabolic; Metabolism; Methods; Microbe; Milk; Molecular; Monitor; Mothers; Mus; Nature; Nitrofurantoin; Obesity; Outcome; Pharmaceutical Preparations; Protein Isoforms; Regulation; Role; Sampling; Series; Skin; Swab; Therapeutic; Time; enzyme activity; experimental study; human data; infant monitoring; innovation; innovative technologies; insight; mature animal; metabolome; metabolomics; microbial; microbiome; microbiome alteration; microbiome analysis; microbiome composition; non-invasive monitor; pharmacometrics; research study

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.

项目总结 该数据科学项目提案寻求在无目标的情况下利用创新方法 代谢组学和微生物组分析研究母体接触抗生素的影响 哺乳婴儿。当母乳喂养的母亲服用抗生素治疗常见感染时， 婴儿的微生物群及其代谢可能会受到影响。这可能会是长期的 对婴儿整体健康的影响，因为微生物群在 健康和疾病。由于婴儿体内的药物浓度较低，因此很难监测药物对婴儿的影响 血容量和抽血的侵袭性。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监测新方式 婴儿用药。本项目将调查的三个领域是： 目标1：通过监测婴儿通过母乳接触抗生素的水平 使用非侵入性拭子的皮肤代谢组。我们将测试母乳喂养的婴儿的皮肤 母亲服用了抗生素，母乳喂养了母亲没有服用的婴儿 抗生素，以及母亲服用抗生素的非母乳喂养的婴儿 项目1.非靶向代谢组学和分子网络将用于检测抗生素 以及它们在皮肤中的代谢物。 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。 从项目1获得的婴儿粪便样本将进行分析，以确定微生物群是否发生了变化 从母亲那里得到的抗生素。我们将比较四种不同的抗生素是如何在 临床研究对婴幼儿微生物组和代谢组的影响。 目的3：从直接和间接两个方面阐明幼鼠的肠道代谢变化 (通过产妇治疗或母乳喂养)接触氨苄西林，并调查宿主 细胞色素P450(CYP)活性发生改变。从项目2获得的鼠标样本将 使用新的数据科学应用程序进行分析，以确定氨苄西林的效果 母乳对婴儿整个肠道和肝脏代谢的影响 细胞色素P450药物代谢酶(Cyp)。我们还将有针对性地分析 来自我们的药物计量和分析化学核心的母乳中的氨苄西林 牛奶分析核心的母乳分析，以补充我们无针对性的方法。 我们还将评估氨苄西林对小鼠肠道和肝脏中Cyp活性的影响。