Human colitis-associated colorectal carcinoma progression is accompanied by dysbiosis with enriched pathobionts

Dysbiosis in inflammatory bowel disease (IBD), including pathobiont colibactin-producing (pks+) Escherichia coli, contributes to inflammation and risk of colitis-associated carcinoma (CAC) in animal models. We aimed to identify microbiome and pathobiont differences in human CAC compared to longstanding non-neoplastic IBD and CRC. Twenty-four CAC resections were matched with CRC and IBD controls for gender, anatomic location, stage, IBD diagnosis, and IBD duration. Pathology was reviewed for stage, tumor-infiltrating leukocytes, and activity scores. 16S rDNA was sequenced from mucosal margins, primary tumors, and metastases. Alpha diversity was assessed with several indices, beta diversity with Bray-Curtis dissimilarity, and individual taxa with linear discriminant analysis (LDA). Pathobionts were quantified with qPCR. Survival outcomes were assessed with log-rank proportional hazards testing.