Bacteria associated with peritoneal metastasis of Pseudomyxoma Peritonei

Distinct microbial communities are commonly found colonizing the tumor microenvironment of multiple cancer types. Pseudomyxoma Peritonei (PMP) is a cancer characterized by the spread of mucus-secreting epithelial cells throughout the peritoneal cavity. Typically originating from the rupture of an appendiceal neoplasm, these peritoneal metastases have a clear path of exposure to gut microbes. Previous work has shown that PMP tumors harbor a distinct microbial community that may represent a therapeutic target. However, that work did not control for the potential contamination of these low microbial biomass samples. Thus, we expand upon these prior findings by characterizing the microbiome of 70 additional PMP tumors and 6 normal peritoneal control tissues along with appropriate laboratory controls. Additionally, DNA from a subset of 25 samples was extracted and sequenced at an independent laboratory. High-quality samples with low contamination were identified via a multistep quality assessment workflow. Robust and reproducible microbial signatures were identified by comparing unique bacterial sequences shared between high-quality tumor replicates. 23% of PMP tumor and 40% of control peritoneal tissue extractions passed an initial quality assessment. We found evidence of reproducible microbial signatures between 6 paired PMP tumor replicates that have previously been linked to colorectal cancer. While we found that Proteobacteria, ??Actinobacteria, Firmicutes, and Bacteroides were present in most PMP tumors, we observed that tumor-associated bacterial communities were predominantly patient-specific at the ASV level. Our findings demonstrate how independent sample replication can be a powerful approach to investigate low-biomass microbial communities associated with tumor and normal tissue samples.