Comparative genomics of the skin microbiome and associated isolates of patients undergoing mastectomy with immediate breast reconstruction

Mastectomy with immediate breast reconstruction (IBR) is an increasingly common component of breast cancer treatment; however, these procedures carry a substantial risk of surgical site infections (SSIs) and noninfectious wound complications (NIWCs). We hypothesized that the local skin microbiota may contribute to the development of post-operative complications, in part by serving as a reservoir for pathobionts, such as Staphylococcus epidermidis and Cutibacterium acnes. We collected skin and intraoperative samples from 60 patients undergoing mastectomy with IBR. To evaluate longitudinal shifts in community composition, we performed 16S rRNA gene sequencing of 151 breast and axilla skin swabs collected at pre- and post-operative timepoints. We also selectively cultured 232 S. epidermidis and 130 C. acnes isolates from skin swabs, implant swabs, and seroma fluid, which were extensively characterized following whole genome sequencing. We observed perturbations to community structure in the breast and axilla following mastectomy. These shifts did not resolve in patients that developed an SSI, which were characterized by a significant enrichment of Bacillus spp. We also uncovered outcome-specific genomic signatures in S. epidermidis and C. acnes isolates, which may offer mechanistic insight into the role of these species in SSI and NIWC development. Importantly, we also identified genomic signatures that are detectable prior to mastectomy and infection diagnosis that may offer clinical utility towards predicting post-operative complications. Together, these findings illustrate the importance of the skin microbiome in SSI and NIWC development following mastectomy with IBR.