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.

项目概要/摘要 人类在饮食和环境中不断遇到微生物，但只占其中的一小部分 微生物在成人肠道微生物组中长期居住。微生物疗法，如益生菌和 粪便微生物群移植通常试图引入新的、理想的微生物，但这些菌株经常被 迷失并且无法稳定地殖民现有社区。了解影响的生态相互作用 定植和传播对于设计成功的靶向微生物组疗法至关重要。生态的 理论预测，交叉喂养、营养竞争和优先效应等因素可能会影响 新的微生物在已建立的群落中定居，但生态相互作用的例子仍然很少 影响人类肠道微生物组的定植。在这里，我们建议研究生态相互作用 影响自然和实验肠道微生物定植和传播的微生物群落 社区。我们计划重点关注家庭，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来记录成人接触抗生素后的传播情况 肠道微生物组使我们能够确定干扰如何影响菌株定植。我们还将使用一个 新颖的实验系统，用于测试群落多样性、生态漂移等生态因素的作用 环境扰动。首先，我们将追踪家庭内人类肠道内的传播事件 通过对粪便样本进行宏基因组测序来暴露抗生素后的微生物组 家庭队列。通过分析这些数据，我们将识别之前和之后发生的传输事件 抗生素暴露，我们将追踪菌株传播后出现的突变轨迹，如菌株 在新的宿主和社区中传播。接下来，我们将描述生态漂移和群落的影响 离体微生物群落传播的多样性。我们从粪便中产生了离体群落 从我们的家庭队列中收集样本，我们将混合成对的社区来评估 菌株剂量和传播的群落多样性。最后，我们将系统地混合离体社区 以确定在抗生素干扰之前和之后能够在群落中定殖的菌株。共同完成这项工作 将提供有关影响微生物定植的生态因素的重要新信息 传播。这里提出的初步探索性工作也将为使用这些的未来工作铺平道路 肠道衍生群落的集合，用于识别和表征之间的分子和代谢相互作用 影响微生物定植的菌株，帮助我们设计更有效、更有针对性的微生物疗法。