Surgical site infections and the microbiome: Understanding the pathogenesis of surgical site infections

项目摘要 手术部位感染（SSI）是最常见的医院获得性感染， 死亡率增加，住院时间增加9.7天，每年花费35 - 100亿美元。 有无数的技术被实施来降低SSI的发生率，重点是减少皮肤病原体。 然而，如果致病菌来自胃肠道（GI）而不是皮肤植物群，这些预防性药物可能会导致皮肤感染。 干预措施可能不足以减少或消除SSI。缺乏对细菌来源的了解 病原体限制了我们个性化SSI预防方法的能力。 越来越多的证据表明宿主微生物组与SSI的发展有关。目前的证据 表明皮肤和GI微生物群的多样性可能更能预测SSI的发展， 更传统的SSI预测器。这些微生物群代表了针对皮肤和胃肠道的有意义的机会 将生态失调作为预防SSI的策略。 这项研究的总体目标是通过针对特定人群的干预措施来预防SSI。 病原体的来源和优化宿主微生物环境。核心假设是， 的皮肤和切口微生物群是预测SSI发病机制。假设将通过2 明确的目标。1)首先，该研究旨在确定切口部位微生物群落的多样性是否 与SSI的发展相关，通过测量的多样性和微生物群落组成的 在手术过程中的不同时间点的切口微生物组。将从300名患者中采集样本 接受开放式胃肠道手术将使用16 S RNA进行病例对照研究，比较α多样性 30例发生SSI的患者与30例年龄、性别、诊断和伤口类型的患者进行了测序比较， 未发生SSI的匹配对照患者。2)接下来，该研究旨在确定致病菌株是否 手术时皮肤或GI微生物群中存在引起SSI的细菌。细菌菌株 从20名发生SSI的患者亚组（来自目标1中收集的样本）中分离的病毒将使用 鸟枪宏基因组学下一步，鸟枪宏基因组学将用于确定特定的菌株是否 在手术前即刻，皮肤和/或胃肠道中存在细菌。 这是一项创新的合作研究，旨在评估SSI与微生物组之间的关联。 由于SSI是一个全球性问题，这些发现具有全球影响和影响。结果是 这项研究将提供有关SSI发病机制的重要机制细节，以及病原体是否 在手术时存在于皮肤或胃肠道。这些结果将用于指导干预性研究 针对影响SSI发展的可改变的微生物群特征。这项研究是必要的第一步 在进行前瞻性、干预性临床试验之前，这些试验可用于强调靶向SSI 基于微生物群落的预防。

Project Summary Surgical sites infections (SSIs) are the most common hospital-acquired infection and result in 2 to 11-fold increased mortality, an additional 9.7 days of hospital stay, and annual costs of 3.5 – 10 billion U.S. Dollars. There are myriad techniques implemented to reduce rates of SSIs focusing on reducing skin pathogens. However, if pathogenic bacteria arise from the gastrointestinal (GI) tract rather than skin flora, these preventive interventions may be inadequate to reduce or eliminate SSIs. A lack of knowledge of the source of bacterial pathogens limits our ability to personalize approaches to SSI prevention. There is a growing body of evidence linking the host microbiome to SSI development. Current evidence suggests that skin and GI microbiota diversity may be more predictive of SSI development compared with more traditional SSI predictors. These microbiomes represent a meaningful opportunity to target skin and GI tract dysbiosis as a strategy to prevent SSI. The overarching goal of this research aims to prevent SSIs through interventions targeting the specific source of pathogens and optimizing the host microbial environment. The central hypothesis is that the diversity of the skin and incisional microbiota is predictive of SSI pathogenesis. The hypothesis will be tested through 2 specific aims. 1) First, the study aims to determine if diversity in microbial communities at the incision site is associated with development of SSI by measuring the diversity and microbial community composition of the incisional microbiome at different time points during surgery. Samples will be collected from 300 patients undergoing open GI surgery. A case-control study will be performed comparing alpha diversity using 16S RNA sequencing in 30 patients who develop SSI compared with 30 age-, sex-, diagnosis-, and wound class- matched control patients who do not develop SSI. 2) Next, the study aims to determine if pathogenic strains of bacteria causing SSI are present in the skin or GI microbiota at the time of operation. The strain of bacteria isolated from a subset of 20 patients who develop SSI (from samples collected in Aim 1) will be identified using shotgun metagenomics. Next, shotgun metagenomics will be used to determine whether that specific strain of bacteria was present in the skin and/or GI tract immediately prior to operation. This is innovative and collaborative research assessing the association between SSIs and the microbiome. As SSIs are a global concern, these findings with have global implications and impact. The results from this study will provide important mechanistic details regarding SSI pathogenesis and whether pathogens are present at the skin or GI tract at the time of operation. These results will be used to guide interventional studies targeting modifiable microbiota features that influence SSI development. This study is the first necessary step before performing prospective, interventional clinical trials which can be designed to underscore targeted SSI prevention based on microbial communities.