Translational Research to Prevent and Control Global Infectious Diseases (Translational Global Infectious Diseases Research Center, TGIR).

摘要 人类肠道微生物群是包括免疫应答在内的许多生理过程的可改变效应物。 减毒活口服疫苗刺激肠道粘膜表面的免疫力，这是一种充满免疫力的微环境。 生活在复杂的相互作用和动态进化的社区中的各种微生物类群。证据表明 肠道微生物组是口服疫苗反应中观察到的一些差异的原因， 在资源有限的情况下，疾病预防工作面临挑战，但仍存在许多知识差距。 了解肠道微生物组对口服疫苗反应的影响是克服两个最重要的问题的关键。 全球儿科公共卫生的关键问题：根除脊髓灰质炎，如果成功，将成为 最伟大的全球公共卫生成就;轮状病毒，一种疫苗可预防的腹泻原因， 导致每年超过10万名儿童死亡我们组建了一个跨学科的团队， 现任和前任COBRE项目领导人从佛蒙特大学的翻译全球传染病 疾病研究中心（TIGR）和达特茅斯学院的分子流行病学中心。这支球队将 开展一个新项目，旨在评估肠道微生物组在口服疫苗接种和反应中的作用， 建立在现有的研究主题，并利用两个中心的资源。我们的新合作项目 将创建丰富的宏基因组数据集，这些数据集来自现有的疫苗试验， 疫苗反应生物标志物已经测量。对于这些数据，我们将应用已建立的生物统计学 方法，并开发和应用一种新的机器学习方法来识别微生物组的特征 与保护性和粘膜免疫反应的发展有关。该项目将产生数据， 为随后的长期研究提供关于口服疫苗应答中主要持续问题的信息， 微生物-宿主界面的复杂系统。

ABSTRACT The human gut microbiota is a modifiable effector of many physiological processes including immune response. Live attenuated oral vaccines stimulate immunity at the gut mucosal surface, a microenvironment teeming with diverse microbial taxa living in complex interacting and dynamically evolving communities. Evidence suggests that the gut microbiome is responsible for some of the differences observed in oral vaccine response that challenge disease prevention efforts in resource-limited settings, but many knowledge gaps remain. Understanding the effects of the gut microbiome on oral vaccine response is key to overcoming two of the most critical problems in pediatric global public health: polio eradication, which, if successful, would be among the greatest global public health achievements; and rotavirus, a vaccine-preventable cause of diarrhea still responsible for well over 100,000 pediatric deaths per year. We have assembled an interdisciplinary team of current and former COBRE Project Leaders from University of Vermont’s Translational Global Infectious Diseases Research (TIGR) Center and Dartmouth College’s Center for Molecular Epidemiology. This team will take on a new project aimed at evaluating the role of the gut microbiome in oral vaccine take and response that builds upon existing research themes and leverages the resources of both centers. Our new collaborative project will create rich metagenomic data sets of longitudinal stool sampling from existing vaccine trials with multiple vaccine response biomarkers already measured. To these data, we will apply established biostatistical approaches and develop and apply a novel machine learning approach to identify features of the microbiome related to development of protective and mucosal immune responses. This project will result in data that can inform subsequent long-term investigations of major ongoing questions in oral vaccine response as a function of the complex systems at the microbiome-host interface.