The Cancer-Associated Microbe Library reveals functional host-microbe interactions during colorectal cancer progression

Functional characterization of microbes which colonize CRC is impeded by a lack of bacterial strains from tumor tissues. Here, we report the Cancer-Associated Microbe Library (CAM-L), comprising more than 3,000 viable bacterial isolates, representing 121 distinct species, and 60 matching organoid models from colorectal adenomas, adenocarcinomas, metastases, and adjacent tissue controls of 45 patients. CAM-L comprises 47 species not covered by large stool-based culture collections and two novel species of Fusobacterium and Granulicatella. In silico characterization reveals that CAM-L isolates encode a diversity of host-relevant functions that differ by disease state. We showcase the capacity for functional exploration with CAM-L isolates using three examples, covering adhesin variants of genotoxic Escherichia coli, bile salt deconjugation by metastasis-dwelling Enterococcus faecalis and glycoprotein modification by Clostridium perfringens. The CAM-L collection is set to help cancer microbiome research mature from association to systematic exploration of causality.