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

项目总结/摘要 依据：艰难梭菌（C. difficile）感染对老年人的影响， 受影响的患者主要来自长期护理机构（LTCF）。CDI的40%至50% 病例现在来自LTCF，这些设施内的定植率仍然很高， 居民被C.在任何时候都很难。运输C。difficile是一个有据可查的 新的CDI案件的来源，但缺乏管理运送的方法，以防止CDI。 一个日益引起当代关注并成为预防战略目标的因素是， 人类微生物组。观察长期护理的老年居民如何获得确定的细菌种群， 与增加的脆弱性有关，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， 有针对性的干预措施，以防止CDI的蔓延。候选人：作为紧急情况助理教授 医学在马萨诸塞州医学院，PI已发表了原始调查 描述了养老院老人肠道内的生态失调模式， 药物与CDI风险增加有关。PI的短期目标是获得先进的 老年医学和微生物科学培训。该培训计划和拟议的研究 该项目将促进PI的发展，作为一个独立的，联邦政府资助的，老龄化的研究人员，其职业生涯 将侧重于预防护理之家老年人的保健相关疾病。研究： 我们假设老年患者肠道微生物组的宏基因组谱发生了显著变化， 在进入LTCF后，他们患C.很难这一假设将得到解决 具体目的如下：（1）表征肠道中发生的宏基因组变化， 新入住LTCF的老年居民的微生物组;（2）表征宏基因组变化， 发生在LTCF居民，以确定哪些因素与居民成为C。艰难携带者; 以及（3）比较过渡到LTCF护理的患者与其室友的微生物组变化 微生物组概况。该提案有可能影响CDI日益严重的公共卫生问题， 老年LTCF居民通过未来的R 01资助的调查，重点是新的技术，以预测和 预防C. LTCF老年人群中的艰难携带和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.