The elderly gut microbiome during transition to long-term care and the risk of Clostridium difficile carriage

项目摘要/摘要 理论基础：艰难梭菌感染对老年人群的影响不成比例。 受影响的患者主要来自长期护理机构(LTCFs)。40%至50%以上的CDI 病例现在来自LTCFs，这些设施内的殖民率仍然很高，多达一半 在任何给定的时间被艰难梭菌殖民的居民。艰难梭菌的携带是一种有充分记录的 新的CDI病例的来源，但缺乏管理运输作为预防CDI的一种手段的办法。 一个日益引起当代关注并成为预防战略目标的因素是 人类微生物群。观察长期护理的老年居民如何获得确定的细菌种群 都与身体虚弱有关，并导致疾病风险增加，我们需要更好地了解 随着老年人进入长期护理为奠定基础而发生变化的微生物组因素 有针对性的干预措施，以防止CDI的传播。应聘者：担任急诊学助理教授 在马萨诸塞大学医学院，PI发表了最初的研究 描述疗养院老人肠道内的反生菌模式及其不同之处 药物治疗会增加CDI的风险。PI的短期目标是获得先进的 老年医学和微生物组科学方面的培训。本培训计划和拟议的研究 该项目将促进国际和平研究所发展成为独立的、由联邦政府资助的老年研究人员，其职业生涯 将重点放在预防养老院老年人口的医疗保健相关疾病上。研究： 我们假设老年患者肠道微生物组的元基因组图谱发生了显著变化 在进入LTCF后，他们感染艰难梭菌的风险增加。这一假设将会得到解决。 在以下具体目标中：(1)描述在肠道中发生的元基因组变化 新入院的老年居民的微生物组；(2)描述新入院的老年居民的元基因组变化 在LTCF居民中发生，以确定哪些因素与居民成为艰难梭菌携带者有关； 以及(3)将过渡到LTCF护理的患者与其室友的微生物群变化进行比较 微生物组图谱。这项提议有可能影响疾控中心日益严重的公共卫生问题 LTCF老年居民通过未来的R01资助研究，重点是新的技术来预测和 在LTCF老年人群中预防艰难梭菌携带和CDI。

Project Summary/Abstract Rationale: Clostridium difficile (C. difficile) infection disproportionally affects the elderly population with a predominance of patients affected being from long-term care facilities (LTCFs). Upwards of 40 to 50% of CDI cases are now from LTCFs and colonization rates remain high within these facilities, with as many as half of the residents being colonized with C. difficile at any given time. Carriage of C. difficile is a well documented source of new CDI cases, however approaches to managing carriage as a means to prevent CDI are lacking. One factor that has become of increasing contemporary interest and a target of preventive strategies is the human microbiome. Seeing how elderly residents in long-term care gain a defined population of bacteria that are associated with increased frailty and lead to an increased risk of disease, we need a better understanding of the microbiome factors that change as an elder moves into long-term care in order to lay the foundation for targeted interventions to prevent the spread of CDI. Candidate: As an Assistant Professor of Emergency Medicine at the University of Massachusetts Medical School, the PI has published original investigations describing the dysbiotic patterns seen within the intestines of nursing home elders and how different medications are associated with an increased risk of CDI. The PI's short-term goals are to gain advanced training in geriatric medicine and the microbiome sciences. This training program and proposed research project will facilitate the PI's development as an independent, federally-funded, aging researcher whose career will be focused on preventing healthcare-associated diseases in nursing home elderly populations. Research: We hypothesize that significant shifts in the metagenomic profiles of the older patient's gut microbiome occur after admission to an LTCF that place them at increased risk for C. difficile. This hypothesis will be addressed in the following Specific Aims: (1) to characterize the metagenomic changes that occur in the intestinal microbiome of elderly resident newly admitted to an LTCF; (2) to characterize the metagenomic changes that occur in LTCF residents to identify which factors are associated with a resident becoming a C. difficile carrier; and (3) to compare the microbiome changes in patients transitioning to LTCF care to their roommates microbiome profile. This proposal has the potential to impact the growing public health problem of CDI in elderly LTCF residents through future R01 funded investigations focusing on novel techniques to predict and prevent C. difficile carriage and CDI in the LTCF elderly population.