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REVIEW article

Front. Cell. Infect. Microbiol.
Sec. Intestinal Microbiome
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1458033
This article is part of the Research Topic New Insights into Gut Microbiota in Colorectal Cancer View all articles

Direct and indirect effects of estrogens, androgens and intestinal microbiota on colorectal cancer

Provisionally accepted
Zihong Wu Zihong Wu Zihong Wu Zihong Wu Renyi Zhang Renyi Zhang Fengming You Fengming You Xueke Li Xueke Li *Chong Xiao Chong Xiao *
  • Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China

The final, formatted version of the article will be published soon.

    Sex differences in colorectal cancer (CRC) has received considerable research attention recently, particularly regarding the influence of sex hormones and the intestinal microbiota. Estrogen, at the genetic and epigenetic levels, directly inhibits CRC cell proliferation by enhancing DNA mismatch repair, regulating miRNAs, blocking the cell cycle, and modulating ion channels. However, estradiol's activation of GPER promotes oncogene expression. Conversely, androgen contributes to epigenetic dysregulation and CRC progression via nuclear receptors while inducing apoptosis through membrane receptors. Specific gut microorganisms produce genotoxins and oncogenic metabolites that damage colonic cell DNA and contribute to cancer induction. Regarding the tumor microenvironment, estrogen mitigates intestinal inflammation, reverses immunosuppression, increases gut microbiome diversity and commensal bacteria abundance, and decreases pathogen enrichment. On the contrary, androgen disrupts intestinal microecology, diminish immunotherapy efficacy, and exacerbate colonic inflammation and tumor growth. The impact of estrogen and androgen is closely tied to their receptor status, elucidating their dual roles in CRC pathogenesis. This review comprehensively discusses the direct and indirect effects of sex hormones and the intestinal microbiota on CRC, considering environmental factors such as diet and lifestyle to propose novel prevention and treatment strategies.

    Keywords: colorectal cancer, Estrogens, Androgens, intestinal microbiota, direct and indirect effects

    Received: 01 Jul 2024; Accepted: 04 Nov 2024.

    Copyright: © 2024 Wu, Wu, Zhang, You, Li and Xiao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xueke Li, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
    Chong Xiao, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.