Household transmission of the human gut microbiota after antibiotic exposure

项目摘要/摘要 人类经常在饮食和环境中遇到微生物，但只有一小部分 微生物长期居住在成人肠道微生物群中。微生物组疗法，如益生菌和 粪便微生物区系移植通常试图引入新的、令人满意的微生物，但这些菌株经常是 迷失并未能稳定地殖民现有社区。了解影响环境的生态相互作用 定植和传播是设计成功的靶向微生物组疗法的关键。生态 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 会影响人类肠道微生物群的定植。在这里，我们建议研究生态相互作用在 影响肠道自然微生物和实验肠道微生物定植和传播的微生物群落 社区。我们计划将重点放在家庭上，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 肠道微生物群，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，用于测试生态因素的作用，如群落多样性、生态漂移和 环境扰动。首先，我们将跟踪家庭内人类肠道的传播事件 抗生素暴露后的微生物组，通过对来自 家庭队列。通过分析这些数据，我们将识别发生在之前和之后的传输事件 抗生素暴露，我们将跟踪菌株传播后出现的突变的轨迹，作为菌株 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。 在体外微生物群落中传播的多样性。我们已经从粪便中产生了体外群落 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 菌株剂量和群落多样性对传播的影响。最后，我们将系统地混合体外群落 鉴定在抗生素干扰前后能够在群落中定居的菌株。共同努力，这项工作 将提供关于形成微生物定殖化的生态因素和 变速箱。这里提出的初步探索性工作也将为使用这些技术的未来工作铺平道路 肠道来源的群落集合，以识别和表征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组疗法。

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.