Analysis of <i>Fusobacterium</i> persistence and antibiotic response in colorectal cancer

Abstract

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