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Fusobacterium nucleatum and the Immune System in Colorectal Cancer

  • Elena Monica Borroni
  • Dorina Qehajaj
  • Floriana Maria Farina
  • Daniel Yiu
  • Robert S. Bresalier
  • Maurizio Chiriva-Internati
  • Leonardo Mirandola
  • Sanja Štifter
  • Luigi Laghi
  • Fabio GrizziEmail author
Nutrition and Nutritional Interventions in Colorectal Cancer (K Wu, Section Editor)
  • 24 Downloads
Part of the following topical collections:
  1. Topical Collection on Nutrition and Nutritional Interventions in Colorectal Cancer

Abstract

Purpose of Review

To summarize the relationship between colorectal cancer (CRC), immunity, and the gut microbiome, focusing on the population of Fusobacterium, particularly Fusobacterium nucleatum, which may mediate CRC initiation and progression by inhibiting host anti-tumor immunity.

Recent Findings

The onset and advancement of CRC involves genetic and epigenetic alterations and are modified by dietary and environmental factors. There is increasing evidence suggesting that gut bacteria, such as Fusobacterium nucleatum, may promote CRC development. The mechanisms through which Fusobacterium nucleatum from the oral cavity colonizes the gut mucosa and affect CRC development and progression remain unclear. Data from metagenomics analyses have shown an enrichment of Fusobacterium nucleatum in CRC tissues, which has been confirmed by quantitative PCR for the 16S ribosomal RNA gene DNA sequence of Fusobacterium nucleatum. Recent studies also suggest that Fusobacterium nucleatum may preferentially bind to cancerous cells, aided by Annexin A1, specifically expressed in proliferating CRC cells. This is consistent with a previous report that although Fusobacterium nucleatum is detected in both colorectal adenoma and adenocarcinoma tissues, the fadA gene levels are significantly higher in the latter than in the former. Other potential mechanisms include the ability of Fusobacterium to produce cancer-associated metabolites or genotoxic factors and possibly a direct interaction with the host immune system. Supporting a possible interaction with the host immune system are recent data indicating that overload of Fusobacterium nucleatum elicits high levels of Fusobacterium nucleatum-specific antibodies in CRC patients, suggesting that Fusobacterium nucleatum may escape host humoral immune responses by evolving inside host cells. Additionally, it has been found that the interaction of Fusobacterium nucleatum with immune response to CRC differs by tumor microsatellite (MS) status, suggesting that Fusobacterium nucleatum and MS status interact to influence anti-tumor immune functions.

Summary

The current literature suggests that Fusobacterium nucleatum, a Gram-negative oral anaerobe, may significantly contribute to CRC development. Furthermore, the presence of Fusobacterium nucleatum in CRCs has also been associated with MSI-high status, lower levels of infiltrating T-lymphocytes, and poor clinical outcomes. We believe that the integration of new technologies, including genomics, bioinformatics and systems medicine, may help to better understand how Fusobacterium nucleatum, immunity status, and environmental factors interact in the initiation and progression of CRCs and generate further information regarding prognostic and therapeutics options for this tumor.

Keywords

Colorectal cancer Fusobacterium nucleatum Immunity Microbiome, diet 

Notes

Acknowledgments

The authors are grateful to Teri Field for her editorial support.

Authors’ Contributors

Borroni EM, Qehajaj D, Farina FM, Yiu D, Bresalier RS, Chiriva-Internati M, Mirandola L, Stifter S, Laghi L, Grizzi F: drafted and discussed the manuscript and approved the final version.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Elena Monica Borroni
    • 1
    • 2
  • Dorina Qehajaj
    • 3
  • Floriana Maria Farina
    • 1
    • 2
  • Daniel Yiu
    • 4
  • Robert S. Bresalier
    • 5
  • Maurizio Chiriva-Internati
    • 5
    • 6
    • 7
  • Leonardo Mirandola
    • 7
  • Sanja Štifter
    • 8
  • Luigi Laghi
    • 9
    • 10
  • Fabio Grizzi
    • 3
    • 11
    Email author
  1. 1.Department of Biotechnology and Translational MedicineUniversity of MilanMilanItaly
  2. 2.Department of Leukocyte BiologyHumanitas Clinical and Research CenterMilanItaly
  3. 3.Department of Immunology and InflammationHumanitas Clinical and Research CenterMilanItaly
  4. 4.Department of General SurgeryFrimley Health NHS Foundation TrustSloughUK
  5. 5.Department of Gastroenterology, Hepatology and Nutrition, Division of Internal MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA
  6. 6.Department of Lymphoma and MyelomaThe University of Texas MD Anderson Cancer CenterHoustonUSA
  7. 7.Kiromic Inc.HoustonUSA
  8. 8.Department of PathologyClinical Hospital Center RijekaRijekaCroatia
  9. 9.Department of GastroenterologyHumanitas Clinical and Research CenterMilanItaly
  10. 10.Hereditary Cancer Genetics ClinicHumanitas Clinical and Research CenterMilanItaly
  11. 11.Histology CoreHumanitas Clinical and Research CenterMilanItaly

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