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: 10681299
• 负责人: Shirley M Tsunoda
• 金额: $ 21.04万
• 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/10681299
• 关键词: Adult; Affect; Amoxicillin; Ampicillin; Analytical Chemistry; Animals; 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; Dedications; 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; Microsomes; 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; 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.

项目概要 该数据科学项目提案旨在利用创新方法进行非针对性的研究 代谢组学和微生物组分析研究母体抗生素暴露的影响 母乳喂养的婴儿。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新陈代谢可能会受到影响。这可能会长期 由于微生物组在婴儿的整体健康中发挥着重要作用，因此对婴儿的整体健康产生影响 健康和疾病。由于婴儿体内的药物浓度较低，因此很难监测药物的作用。 血量和抽血的侵入性。我们已经能够以非侵入方式 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监控方式 婴儿药物。该项目要调查的三个领域是： 目标 1：通过监测母乳中的婴儿抗生素暴露水平 使用非侵入性拭子进行皮肤代谢组分析。我们将测试母乳喂养婴儿的皮肤 其母亲服用了抗生素，母乳喂养的婴儿其母亲未服用抗生素 抗生素，以及母亲接受抗生素治疗的非母乳喂养婴儿 项目1.非靶向代谢组学和分子网络将用于检测抗生素 及其在皮肤中的代谢物。 目标 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 获得的婴儿粪便样本中微生物组的变化 来自母亲的抗生素。我们将比较四种不同抗生素的使用效果 影响婴儿微生物组和代谢组的临床研究。 目标 3：直接或间接阐明幼年小鼠的肠道代谢转变 （通过产妇治疗或母乳喂养）接触氨苄西林并调查宿主是否 细胞色素 P450 (CYP) 活性发生改变。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作用 母乳对婴儿整个肠道和肝脏的新陈代谢的影响，包括 细胞色素 P450 药物代谢酶 (Cyp)。我们也会有针对性的分析 母乳中的氨苄西林来自我们的药物计量学和分析化学核心以及 来自牛奶分析核心的母乳分析可补充我们的非针对性方法。 我们还将评估氨苄西林对小鼠肠道和肝脏 Cyp 活性的影响。