Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer

Abstract
Colorectal cancers comprise a complex mixture of malignant cells, nontransformed 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 and 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.
Funding Information
  • National Institutes of Health (CA197568)
  • National Institutes of Health (CA197735)
  • National Institutes of Health (CA197735)
  • Prevent Cancer Foundation (Figdor Family Fellowship)
  • National Institute of Health (CA148894)
  • DF/HCC GI SPORE P50 (CA127003)
  • American Cancer Society Research Professorship
  • DF/HCC GI SPORE P50 (CA127003)
  • DF/HCC GI SPORE P50 (CA127003)
  • DF/HCC GI SPORE P50 (CA127003)
  • DF/HCC GI SPORE P50 (CA127003)
  • National Institute of Health (CA205406)
  • DF/HCC GI SPORE P50 (CA127003)
  • National Institute of Health (CA118553)
  • National Institute of Health (CA169141)
  • Cellex Private Foundation
  • Cellex Private Foundation
  • Banco Bilbao Vizcaya Argentaria Foundation
  • Hale Family Center for Pancreatic Cancer
  • Cellex Private Foundation
  • Project P Fund for Colorectal Cancer Research
  • Stand-Up-to-Cancer
  • Chambers Family Fund for Colorectal Cancer Research
  • Team Perry Fund
  • Clark Family Fund for GI Cancer Research
  • Cellex Private Foundation
  • Cellex Private Foundation