The role of gut microbiota in prostate cancer progression - A Mendelian randomization study of immune mediation

Sep 22, 2026

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The potential relationship between gut microbiota and prostate cancer, possibly mediated by immune cells, remains unclear. Using mediation Mendelian randomization, the study assessed causal links among gut microbiota, immune cell activity, and prostate cancer by combining immune cell data and genome-wide association outcomes. Bidirectional analyses applied IVW, weighted median, MR-Egger, weighted mode, and simple mode. Eighty-three prostate-cancer-associated SNPs served as instruments, and mediation testing identified CD39+ Tregs as partial mediators.

LanguageEnglish

CategoryResearch & Report

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Pages7

Reading Time18 min

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Introduction

Background and risk factors

Role of diet and gut microbiota

Interaction between gut microbiota and tumors

® Observational Study The role of gut microbiota in prostate cancer progression A Mendelian randomization study of immune mediation Song Li, MDa ,b ,c , Ruoxuan Liu, MDb ,c , Xuexue Hao, MDa , Xiaoqiang Liu, PhDa ,* | Abstract
The potential relationship between the gut microbiota and prostate cancer, possibly influenced by immune cells, remains unclear. This study employed the mediation Mendelian randomization (MR) technique to investigate the causal link between the gut microbiota, immune cells, and prostate cancer. Data on immune cell activity were sourced from Valeria Orrù’s research, whereas the genome-wide association study outcome dataset was obtained from the Integrative Epidemiology Unit database. The bidirectional MR analysis utilized 5 different methods: inverse variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode. In addition, the mediating effect of immune cells on the gut microbiota and prostate cancer was explored using mediation analysis. Eighty-three single nucleotide polymorphisms associated with prostate cancer were screened as instrumental variables. In a positive MR analysis with gut microbiota as the exposure factor, IVW showed an association between 8 gut microbiota and prostate cancer. Additionally, 9 types of immune cells have been found to be associated with prostate cancer using methods such as IVW. MR analysis of the gut microbiota on immune cells (beta1) revealed a negative correlation between Bifidobacterium and CD39+ T regulatory cells (Tregs; odds ratio [OR] = 0.785, 95% confidence interval [CI]= 0.627–0.983, P = .03) . Furthermore, MR analysis of immune cells in prostate cancer disease (beta2) showed that CD39+Tregs are a risk factor for prostate cancer (OR = 1.215, 95% CI = 1.027–1.354, P = .04) . Moreover, MR analysis of gut microbiota in prostate cancer (total effect) indicated that Bifidobacterium is a protective factor for prostate cancer (OR = 0.905, 95% CI = 0.822–0.977, P = .04) . The sensitivity analysis verified the robustness of the above results. Mediation analysis demonstrated that CD39+Tregs partially mediate the causal relationship between Bifidobacterium and prostate cancer. This study demonstrates that Bifidobacterium inhibits prostate cancer progression through CD39+Tregs as mediators, providing new ideas and approaches for the treatment and prevention of prostate cancer. | | --- | | Abbreviations: CI = confidence interval , GWAS = genome-wide association study, IV = instrumental variables, IVW = inverse variance weighted, MR = Mendelian randomization, OR = odds ratio, Pca = Prostate cancer, SNPs = single nucleotide polymorphisms, Tregs = T regulatory cells, WME = weighted median. | | Keywords: gut microbiota, Mendelian randomization, prostate cancer, Tregs | 1. Introduction Prostate cancer is one of the most common tumors threatening men’s health, and it has the fastest increase in incidence rate at present. [1] Among the relative risk factors for prostate cancer, dietary habits account for an important proportion, and men who frequently consume foods containing high animal fat are at high risk for prostate cancer.[2] From the research results of 32 countries, it was found that the incidence rate of people who eat a diet rich in vegetables and fruits was low. Changes in the composition of gut microbiota can affect dietary compounds and nutrient metabolites related to the risk of prostate cancer.[3] With the development of 16S rRNA sequencing technology, research on gut microbiota has become a hot topic in recent years. Many tumors (such as ovarian cancer, sarcoma, and melanoma), although not directly in contact with the gut microbiota, are also regulated by the gut microbiota during their progression. In mice with melanoma, a high-fat diet can lead to dysbiosis of the gut microbiota, manifested by an increase in Clostridium, which can induce tumor infiltration of melanoma by activating nuclear factor kappa-B signa

FAQs

What method did the study use to test the causal role of gut microbiota and immune cells?

The study used mediation Mendelian randomization (MR) to evaluate causal links between gut microbiota, immune cells, and prostate cancer, including mediation analysis.

Which gut microbiota and immune cell types showed causal associations in MR results?

Positive MR results indicated associations between specific gut microbiota and prostate cancer, while MR analysis of gut microbiota on immune cells identified Bifidobacterium and CD39+ T regulatory cells (Tregs). Immune-cell MR also suggested CD39+ Tregs increased prostate cancer risk.

What did mediation analysis conclude about immune cells as mediators?

Mediation analysis demonstrated that CD39+ Tregs partially mediated the causal relationship between Bifidobacterium and prostate cancer progression.

Sep 22, 2026

Upload by Noah