Household transmission of the human gut microbiota after antibiotic exposure

接触抗生素后人类肠道微生物群的家庭传播

• 批准号: 10593834
• 负责人: DAVID A. RELMAN
• 金额: $ 31.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-07 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10593834
• 关键词: Adult; Affect; Antibiotics; Autologous; Ciprofloxacin; Collection; Communities; Data; Diet; Environment; Event; Exclusion; Feces; Future; Goals; Household; Human; Individual; Maps; Metabolic; Microbe; Molecular; Mutation; Nutrient; Outcome; Predictive Factor; Probiotics; Research; Resources; Role; Shapes; Site; Structure; System; Taxonomy; Testing; Work; cohort; design; dosage; experimental study; fecal transplantation; feeding; gut microbiome; gut microbiota; in vivo; insight; metagenomic sequencing; microbial; microbial colonization; microbial community; microbiome; microbiome therapeutics; novel; recruit; residence; stool sample; success; theories; transmission process

PROJECT SUMMARY/ABSTRACT Humans constantly encounter microbes in their diets and environments, but only a tiny fraction of these microbes take up long-term residence in the adult gut microbiome. Microbiome therapeutics like probiotics and fecal microbiota transplants often seek to introduce new, desirable microbes, but these strains are frequently lost and fail to stably colonize existing communities. Understanding the ecological interactions that affect colonization and transmission is crucial for designing successful targeted microbiome therapeutics. Ecological theory predicts that factors like cross-feeding, nutrient competition, and priority effects may affect the ability of new microbes to colonize established communities, but there remain few examples of ecological interactions that affect colonization in the human gut microbiome. Here, we propose to investigate ecological interactions in microbial communities that affect colonization and transmission in natural and experimental gut microbial communities. We plan to focus on households, which are natural settings of microbial transmission. We have already recruited a longitudinal household cohort to document transmission after antibiotic exposure in the adult gut microbiome which allows us to determine how disturbances affect strain colonization. We will also use a novel experimental system to test the role of ecological factors like community diversity, ecological drift, and environmental perturbations. First, we will track transmission events within households in the human gut microbiome after antibiotic exposure by performing metagenomic sequencing of stool samples from the household cohort. By analyzing these data, we will identify transmission events that occur before and after antibiotic exposure, and we will track the trajectories of mutations that arise after strain transmission, as strains propagate in new hosts and communities. Next, we will characterize the effects of ecological drift and community diversity on transmission in ex vivo microbial communities. We have generated ex vivo communities from stool samples collected from our household cohort, and we will mix pairs of communities to evaluate the effects of strain dosage and community diversity on transmission. Finally, we will systematically mix ex vivo communities to identify strains capable of colonizing communities before and after antibiotic perturbation. Together, this work will provide important new information about the ecological factors that shape microbial colonization and transmission. The initial, exploratory work proposed here will also pave the way for future work that uses these collections of gut-derived communities to identify and characterize molecular and metabolic interactions between strains that affect microbial colonization, helping us design more effective, targeted microbiome therapeutics.

项目摘要/摘要 人类在饮食和环境中不断遇到微生物，但其中只有一小部分 微生物在成年肠道微生物组中占据了长期居住。微生物组治疗药，例如益生菌和 粪便菌群移植通常寻求引入新的，理想的微生物，但这些菌株经常是 丢失，无法稳定地殖民现有社区。了解影响的生态互动 定殖和传播对于设计成功的靶向微生物组治疗剂至关重要。生态 理论预测，诸如交叉进食，营养竞争和优先效应等因素可能会影响 新的微生物殖民社区，但几乎没有生态互动的例子 这会影响人类肠道微生物组的定殖。在这里，我们建议研究中的生态互动 影响自然和实验性肠道微生物的定殖和传播的微生物群落 社区。我们计划专注于家庭的自然环境，这是微生物传播的自然环境。我们有 已经招募了一个纵向家庭队列，以记录成人抗生素暴露后的传播 肠道微生物组，这使我们能够确定干扰如何影响菌株定植。我们还将使用 新的实验系统，以测试社区多样性，生态漂移和生态因素的作用 环境扰动。首先，我们将跟踪人类肠道家庭中的传播事件 抗生素暴露后的微生物组，通过对粪便样品进行元基因组测序 家庭队列。通过分析这些数据，我们将确定在之前和之后发生的传输事件 抗生素暴露，我们将跟踪应变后应变后出现的突变的轨迹 在新的主人和社区中传播。接下来，我们将表征生态漂移和社区的影响 离体微生物群落传播的多样性。我们已经从粪便产生了离体社区 从我们的家庭队列中收集的样本，我们将混合成对的社区来评估 应变剂量和传播的社区多样性。最后，我们将系统地混合离体社区 确定能够在抗生素扰动之前和之后殖民社区的菌株。在一起，这项工作 将提供有关塑造微生物定植和的生态因素的重要新信息 传播。这里提出的最初的探索性工作还将为使用这些工作的未来工作铺平道路 肠道衍生的社区的集合，以识别和表征分子和代谢之间的相互作用 影响微生物定植的菌株，帮助我们设计更有效的有针对性的微生物组疗法。