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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Metabolism
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1466190
This article is part of the Research Topic Metabolism, Gut Microbiome, and Cancer View all 8 articles

Gut Microbiota, Metabolites, and Cytokines in Relation to the Risk of Prostate Cancer in the Asian population

Provisionally accepted
Zhengshi Wang Zhengshi Wang Haotian Chen Haotian Chen Yongqiang Liu Yongqiang Liu Libin Zou Libin Zou Zhang Zhijin Zhang Zhijin Zhiqiang Yin Zhiqiang Yin Shiyu Mao Shiyu Mao Changcheng Guo Changcheng Guo Bin Yang Bin Yang Pengfei Wu Pengfei Wu Xudong Yao Xudong Yao *
  • Shanghai Tenth People's Hospital, Tongji University, Shanghai, China

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

    Purpose: Studies have shown that gut microbiota is involved in the tumorigenesis and development of prostate cancer. We aimed to perform a comprehensive analysis of causal associations of gut microbiota, metabolites, and cytokines with prostate cancer in the Asian population. Patients and Methods: Genome-wide association study (GWAS) summary datasets were collected from the public databases. There were 418 bacterial traits, 452 metabolites, 91 cytokines, 5408 cases of prostate cancer from East Asia, and 109,347 controls included. Mendelian randomization (MR) analyses were performed to investigate their causal relationships. Sensitivity analyses were conducted to test the reliability of MR results. Furthermore, the FinnGen database was used to assess the generalizability of our findings based on Asians. Results: There were a total of 17 bacterial traits, 28 metabolites (including 2 microbiota-associated metabolites), and 9 cytokines to be significantly associated with prostate cancer in Asians (P < 0.05). Further MR analyses of these positive results indicated that G_Ruminococcaceae UCG014/TNFSF10 axis, G_Anaerofilum/TNFRSF14 axis, G_Erysipelotrichaceae UCG003/TNFSF10 axis, and P_Proteobacteria/cholesterol axis were key signaling pathways involved in the progression of prostate cancer. Notably, G_Ruminococcaceae UCG014/TNFSF10 axis and G_Anaerofilum/TNFRSF14 axis were found to act as protective factors, while the other two signaling axes played a crucial role in promoting the progression of prostate cancer. Sensitivity analyses further confirmed the reliability of our findings. Using the European population as outcome, we further assessed the generalizability of our conclusions and found limited applicability to Europeans. Conclusions: We found that there were causal associations of gut microbiota, metabolites, and cytokines with prostate cancer in Asians. The causal effects of gut microbiota on prostate cancer were partially mediated by metabolites and cytokines. These findings might contribute to the development of new therapeutic strategies for prostate cancer.

    Keywords: prostate cancer, GWAS, Gut Microbiota, Single nucleotide polymorphism, cytokine

    Received: 17 Jul 2024; Accepted: 27 Dec 2024.

    Copyright: © 2024 Wang, Chen, Liu, Zou, Zhijin, Yin, Mao, Guo, Yang, Wu and Yao. 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: Xudong Yao, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China

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