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Gut microbiota in colorectal cancer: mechanisms of action and clinical applications

Abstract

Colorectal cancer (CRC) accounts for about 10% of all new cancer cases globally. Located at close proximity to the colorectal epithelium, the gut microbiota comprises a large population of microorganisms that interact with host cells to regulate many physiological processes, such as energy harvest, metabolism and immune response. Sequencing studies have revealed microbial compositional and ecological changes in patients with CRC, whereas functional studies in animal models have pinpointed the roles of several bacteria in colorectal carcinogenesis, including Fusobacterium nucleatum and certain strains of Escherichia coli and Bacteroides fragilis. These findings give new opportunities to take advantage of our knowledge on the gut microbiota for clinical applications, such as gut microbiota analysis as screening, prognostic or predictive biomarkers, or modulating microorganisms to prevent cancer, augment therapies and reduce adverse effects of treatment. This Review aims to provide an overview and discussion of the gut microbiota in colorectal neoplasia, including relevant mechanisms in microbiota-related carcinogenesis, the potential of utilizing the microbiota as CRC biomarkers, and the prospect for modulating the microbiota for CRC prevention or treatment. These scientific findings will pave the way to clinically translate the use of gut microbiota for CRC in the near future.

Key points

  • Colorectal cancer (CRC) is one of the most common cancers; globally, it ranks third in incidence and second in mortality among all cancers.

  • The gut microbiota comprises a large population of microorganisms that interact closely with host intestinal cells, and it can affect the immunity and metabolome in the gastrointestinal tract.

  • According to experimental evidence, the gut microbiota is involved in CRC formation, progression and its response to treatment.

  • Substantial changes in abundance of specific bacteria can be detected in patients with CRC and might serve as biomarkers for disease screening, prognostication and prediction of treatment response.

  • Modulation of the gut microbiota is a promising strategy to enhance treatment efficacy and reduce adverse effects of CRC therapies.

  • Future research should look into the best ways to modulate the gut microbiota and to investigate its short-term and long-term benefits through clinical trials.

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Fig. 1: Microbiota-associated mechanisms involved in the pathogenesis of colorectal cancer.
Fig. 2: Potential clinical applications related to gut microbiota in colorectal cancer.

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Acknowledgements

J.Y. is supported by the Science and Technology Program Grant Shenzhen (JCYJ20170413161534162) and the Health and Medical Research Fund Hong Kong (17160862). Both authors are supported by grants from the CUHK Faculty of Medicine on Microbiota Research and the CUHK Vice-Chancellor’s Discretionary Fund.

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S.H.W. and J.Y. discussed the contents, wrote, reviewed and edited the manuscript.

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Correspondence to Jun Yu.

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Wong, S.H., Yu, J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat Rev Gastroenterol Hepatol 16, 690–704 (2019). https://doi.org/10.1038/s41575-019-0209-8

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