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

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.