Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer

作者：Bullman Susan; Pedamallu Chandra S.; Sicinska Ewa; Claney Thomas E.; Zhang Xiaoyang; Cai Diana; Neuberg Donna; Huang Katherine; Guevara Fatima; Nelson Timothy; Chipashvili Otari; Hagan Timothy; Walker Mark; Ramachandran Aruna; Diosdado Begona; Serna Garazi; Mulet Nuria; Landolfi Stefania; Ramon y Cajal Santiago; Fasani Roberta; Aguirre Andrew J.; Ng Kimmie; Elez Elena; Ogino Shuji; Tabernero Josep; Fuchs Charles S.; Hahn William C.; Nuciforo Paolo; Meyerson Matthew^*

来源：Science, 2017, 358(6369): 1443-+.

DOI：10.1126/science.aa15240

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.

• 出版日期2017-12-15