Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer

By S. Bullman, C. Pedamallu, E. Sicinska, T. Clancy, Xiaoyang Zhang, D. Cai, D. Neuberg, Katherine Huang, F. Guevara, T. Nelson and 19 more. Science, 2017

1,354 citations recorded by the source corpus.

Bacteria go the distance in cancer The bacterial species Fusobacterium nucleatum is associated with a subset of human colorectal cancers, but its role in tumorigenesis is unclear. Studying patient samples, Bullman et al. found that F. nucleatum and certain co-occurring bacteria were present not only in primary tumors but also in distant metastases. Preliminary evidence suggests that the bacterium is localized primarily within the metastatic cancer cells rather than in the stroma. Antibiotic treatment of mice carrying xenografts of F. nucleatum–positive human colorectal cancer slowed tumor growth, consistent with a causal role for the bacterium in tumorigenesis. Science, this issue p. 1443 The same bacteria present in primary tumors of patients with colorectal cancer are also present in liver metastases. 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.

Subfields: Infectious Diseases, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/8063d9d1b997ec13c5549c82162c8ee8a7628d21

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

1. B. Goodman
2. Rob Knight
3. H. Gardner
4. L. Zitvogel
5. J. Wargo

In Molecular Biology

1. Torstein Grønseth
2. B. Goodman
3. R. Simm
4. R. Salazar
5. Rob Knight
6. Jeff Hasty
7. F. Greten
8. H. Gardner

In Neurology

1. F. Greten
2. S. Grivennikov

Citations in the corpus

• The microbiome and human cancer (2021, background): “hematogenous spread (117, 172, 173) or colonized micrometastases (19) may”
• Bacterial Biofilm and its Role in the Pathogenesis of Disease (2020, background): “nucleatum may not be involved in the early stages of carcinogenesis, but may be involved in cancer progression [100,101].”
• Microbiota in health and diseases (2022, result): “For example, Bullman et al. showed that metronidazole treatment can eradicate the colonization of Fusobacterium and ameliorate the progression of CRC.359 The results showed that colonization of Fusobacterium with CRC tumor cells was maintained in distal metastasis, demonstrating a stable microbiome ”
• The microbiome and cancer (2018, background): “These data point to a role for Fusobacterium supporting tumour growth in an immune-independent manner [48].”
• Localised Colon Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. (2020, background): “Some data suggest a putative role in colon cancer carcinogenesis for factors that cause imbalances in gut microbiota.(4,5) The mortality rate in the European Union is 15e20 out of 100 000 in males and 9e14 out of 100 000 in females and has decreased over time, particularly in females.”
• Inflammation and Cancer: Triggers, Mechanisms and Consequences (2019, background): “These microbes and microbial products can even travel with tumors to the site of metastasis and serve as a source of inflammation in metastasis (Bullman et al., 2017).”