Antibiotic Treatment in Breastfeeding Mothers: Effects on Milk, Microbiome, and Infant Outcomes

项目摘要 抗生素的使用在有生育能力的妇女中很常见，包括哺乳期妇女。然而， 已知特定抗生素在母乳中的传播和药代动力学，也不知道 抗生素处理对牛奶组成和质量的影响，包括营养成分、低聚糖特征， 和微生物组。婴儿肠道微生物组的建立依赖于动态的母婴关系 在生命早期，微生物交换在很大程度上是通过母乳喂养促进的。因此，至关重要的是， 了解特定抗生素对牛奶成分的影响。此外，必须确定如何 母亲使用抗生素可能会影响婴儿的结果，包括生长，发育和免疫反应。 在加州圣地亚哥大学人乳研究生物储存库的基础设施上， 高素质的多学科研究团队将前瞻性地招募和采访480对母婴 在基线时，收集乳汁、皮肤和粪便样本，并监测正在进行的母乳喂养实践和母亲使用情况 四种常用抗生素中的一种从这些数据中，我们将随后确定40名产妇/婴儿 母亲接受靶向抗生素治疗的对，40对匹配的母亲/婴儿未接受抗生素治疗 暴露，和20个非哺乳期母亲/婴儿对与目标抗生素治疗的母亲摄取。从 这100对，我们将在3个时间点收集额外的家庭和母婴暴露生物标志物 对应于抗生素开始、中期和末期，收集访谈和医疗记录数据，以及 获得产后12个月婴儿发育的问卷评估。数据将用于 确定母乳样本中目标抗生素的量和药代动力学，并测试中心 假设（1）组间的乳汁成分、低聚糖和微生物组特征存在差异， 抗生素治疗状态;（2）治疗组和未治疗组的微生物组和代谢组学指标不同 母乳喂养组;和（3）抗生素将在粪便，皮肤和家庭环境拭子中检测到， 接受抗生素治疗但未哺乳的母亲。我们还将探讨对产妇的影响 抗生素对婴儿生长发育的影响。 这项研究的发现将填补关于常用抗生素存在的知识的关键空白 以及抗生素治疗对母乳成分和质量的影响， 和长期婴儿结果，包括生长，发育，肠道健康和免疫反应。这将 为制定哺乳期抗生素使用具体指南提供依据，并帮助支持 保健提供者向哺乳妇女提供的建议。

PROJECT SUMMARY Antibiotic use is common among women of reproductive potential, including lactating women. However, little is known about the transmission and pharmacokinetics of specific antibiotics in human milk, nor the effects of antibiotic treatment on milk composition and quality including nutritional components, oligosaccharide profile, and the microbiome. Establishment of the infant gut microbiome is dependent on a dynamic maternal–infant microbiota exchange during early life, which is largely facilitated via breastfeeding. It is thus critical to better understand the impact of specific antibiotics on milk composition. Furthermore, it is essential to determine how maternal antibiotic use may impact infant outcomes, including growth, development, and immune response. Building on the infrastructure of the University of California San Diego Human Milk Research Biorepository, a highly qualified, multidisciplinary research team will prospectively enroll and interview 480 maternal/infant pairs at baseline, collect milk, skin, and stool samples, and monitor ongoing breastfeeding practices and maternal use of one of four commonly used antibiotics over time. From these, we will subsequently identify 40 maternal/infant pairs with maternal uptake of target antibiotic treatment, 40 matched maternal/infant pairs without antibiotic exposure, and 20 non-lactating maternal/infant pairs with maternal uptake of a target antibiotic treatment. From these 100 pairs, we will collect additional home and maternal and infant biomarkers of exposure at 3 timepoints corresponding to antibiotic initiation, mid-course, and end-course, collect interview and medical record data, and obtain a questionnaire assessment of infant development at 12 months post-partum. Data will be used to determine the amount and pharmacokinetics of target antibiotics in breast milk samples and to test the central hypotheses that (1) milk composition, oligosaccharide, and microbiome profiles will differ between groups by antibiotic treatment status; (2) microbiome and metabolomic measures will differ in treated and untreated breastfeeding groups; and (3) antibiotics will be detectable in the stool, skin, and home environment swabs of mothers who are treated with antibiotics but are not breastfeeding. We will also explore the impact on maternal antibiotic use on infant growth and development. Findings of this study will fill a critical gap in knowledge regarding the presence of commonly used antibiotics in breast milk and the effects of antibiotic treatment on both breast milk composition and quality as well as short- and long-term infant outcomes, including growth, development, gut health, and immune response. This will inform evidence-based development of specific guidance on antibiotic use during lactation and help support advice provided by healthcare providers to breastfeeding women.