Gut Microbiota And Metastasis

Remarkably, not only are primary colorectal cancers colonized by particular strains of bacteria from the gut microbiota, but distal metastases of those tumors have the same strains as well.  Therefore, tumor-associated bacteria “go along for the ride” when metastasis occurs; in particular, Fusobacterium nucleatum is associated with both the primary and metastatic tumors, illustrating stability of bacteria-cancer association.  Mouse xenografts of human primary colorectal cancers exhibited maintenance of the bacteria, and antibiotic treatment “reduced Fusobacterium load, cancer cell proliferation and overall tumor growth.”  One wonders if the bacterial actually promote metastasis as well, and are not just “along for the ride;” it would seem reasonable to suppose that at least the bacteria help the metastasis get established and grow at its new location.  All of this highlights the link between gut microbiota and cancer; note also that diet affects the microbiota, possibly in a clinically-relevant manner.  Abstract:

Colorectal cancers comprise a complex mixture of malignant cells, non-transformed cells and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome, including Bacteroides, Selenomonas and Prevotella species, is maintained in distal metastases, demonstrating microbiome stability between paired primary-metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-associated colorectal cancer.