Causal relationship between gut microbiota and prostate cancer contributes to the gut-prostate axis: insights from a Mendelian randomization study

Li Wang; Yong-Bo Zheng; Shan Yin; Kun-Peng Li; Jia-Hao Wang; Er-Hao Bao; Ping-Yu Zhu

doi:10.1007/s12672-024-00925-1

Causal relationship between gut microbiota and prostate cancer contributes to the gut-prostate axis: insights from a Mendelian randomization study

Discov Oncol. 2024 Mar 3;15(1):58. doi: 10.1007/s12672-024-00925-1.

Authors

Li Wang¹, Yong-Bo Zheng¹, Shan Yin¹, Kun-Peng Li², Jia-Hao Wang¹, Er-Hao Bao¹, Ping-Yu Zhu³

Affiliations

¹ Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
² Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China.
³ Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China. zhupingyu@nsmc.edu.cn.

Abstract

Background: Changes in gut microbiota abundance have been linked to prostate cancer development. However, the causality of the gut-prostate axis remains unclear.

Methods: The genome-wide association study (GWAS) data for gut microbiota sourced from MiBioGen (n = 14,306), alongside prostate cancer summary data from PRACTICAL (n = 140,254) and FinnGen Consortium (n = 133,164). Inverse-variance-weighted (IVW) was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl), after diligently scrutinizing potential sources of heterogeneity and horizontal pleiotropy via the rigorous utilization of Cochran's Q test, the MR-PRESSO method, and MR-Egger. We used meta-analysis methods in random effects to combine the Mendelian randomization (MR) estimates from the two sources.

Results: The pooled analyses of MR results show that genus Eubacterium fissicatena (OR = 1.07, 95% CI 1.01 to 1.13, P = 0.011) and genus Odoribacter (OR = 1.14, 95% CI 1.01 to 1.27, P = 0.025) were positively associated with prostate cancer. However, genus Adlercreutzia (OR = 0.89, 95% CI 0.83 to 0.96, P = 0.002), Roseburia (OR = 0.90, 95% CI 0.83 to 0.99, P = 0.03), Holdemania (OR = 0.92, 95% CI 0.86 to 0.97, P = 0.005), Flavonifractor (OR = 0.85, 95% CI 0.74 to 0.98, P = 0.024) and Allisonella (OR = 0.93, 95% CI 0.89 to 0.98, P = 0.011) seems to be a protective factor for prostate cancer. Sensitivity analysis found no significant heterogeneity, horizontal pleiotropy, or reverse causal links in all causal associations.

Conclusion: This MR study lends support to a causal relationship between genetically predicted gut microbiota and prostate cancer. Research on the gut-prostate axis, along with further multi-omics analyses, holds significant implications for the prevention and treatment of prostate cancer.

Keywords: Gene; Gut microbiota; Mendelian randomization; Prostate cancer; Risk.