Colorectal Cancer-Associated Microbiome Patterns and Signatures

Abstract

The gut microbiome is dynamic and shaped by diet, age, geography, and environment. The disruption of normal gut microbiota (dysbiosis) is closely related to colorectal cancer (CRC) risk and progression. To better identify and characterize CRC-associated dysbiosis, we collected six independent cohorts with matched normal pairs (when available) for comparison and exploration of the microbiota and their interactions with the host. Comparing the microbial community compositions between cancerous and adjacent noncancerous tissues, we found that more microbes were depleted than enriched in tumors. Despite taxonomic variations among cohorts, consistent depletion of normal microbiota (members of Clostridia and Bacteroidia) and significant enrichment of oral-originated pathogens (such as Fusobacterium nucleatum and Parvimonas micra) were observed in CRC compared to normal tissues. Sets of hub and hub-connecting microbes were subsequently identified to infer microbe-microbe interaction networks in CRC. Furthermore, biclustering was used for identifying coherent patterns between patients and microbes. Two patient-microbe interaction patterns, named P0 and P1, can be consistently identified among the investigated six CRC cohorts. Characterization of the microbial community composition of the two patterns revealed that patients in P0 and P1 differed significantly in microbial alpha and beta diversity, and CRC‐associated microbiota changes consist of continuous populations of widespread taxa rather than discrete enterotypes. In contrast to the P0, the patients in P1 have reduced microbial alpha diversity compared to the adjacent normal tissues, and P1 possesses more oral-related pathogens than P0 and controls. Collectively, our study investigated the CRC-associated microbiome changes, and identified reproducible microbial signatures across multiple independent cohorts. More importantly, we revealed that the CRC heterogeneity can be partially attributed to the variety and compositional differences of microbes and their interactions to humans.