Abstract

Colorectal cancer (CRC) is highly prevalent, accounting for approximately one-tenth of cancer cases and deaths globally. It stands as the second most deadly and third most common cancer type. Although the gut microbiota has been implicated in CRC carcinogenesis for the last several decades, it remains one of the least understood risk factors for CRC development, as the gut microbiota is highly diverse and variable. Many studies have uncovered unique microbial signatures in CRC patients compared with healthy matched controls, with variations dependent on patient age, disease stage, and location. In addition, mechanistic studies revealed that tumor-associated bacteria produce diverse metabolites, proteins, and macromolecules during tumor development and progression in the colon, which impact both cancer cells and immune cells. Here, we summarize microbiota’s role in tumor development and progression, then we discuss how the metabolic alterations in CRC tumor cells, immune cells, and the tumor microenvironment result in the reprogramming of activation, differentiation, functions, and phenotypes of immune cells within the tumor. Tumor-associated microbiota also undergoes metabolic adaptation to survive within the tumor environment, leading to immune evasion, accumulation of mutations, and impairment of immune cells. Finally, we conclude with a discussion on the interplay between gut microbiota, immunometabolism, and CRC, highlighting a complex interaction that influences cancer development, progression, and cancer therapy efficacy.

Document Type

Article

Publication Date

11-2024

Notes/Citation Information

Copyright © 2024 The Author(s), Published by Wolters Kluwer Health, Inc. This paper is published under Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Digital Object Identifier (DOI)

http://dx.doi.org/10.1097/IN9.0000000000000050

Funding Information

This study was supported in part by the National Institute of Health NIDDK. R56DK136728 (A.A.), P20GM130456 (A.A.; Alam Project ID9790), K01DK114391 (A.A.), ACS IRG (A.A.), and Elsa U. Pardee Foundation Grant (A.A.).

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