Causality investigation among gut microbiota, immune cells, and prostate diseases: a Mendelian randomization study

Abstract

BackgroundThe gut microbiota has been demonstrated to have a significant role in the pathogenesis and progression of a variety of diseases, including prostate cancer, prostatitis, and benign prostatic hyperplasia. Potential links between prostate diseases, immune cells and the gut microbiota have not been adequately investigated.MethodsMR studies were conducted to estimate the effects of instrumental variables obtained from genome-wide association studies (GWASs) of 196 gut microbial taxa and 731 immune cells on the risk of prostate diseases. The primary method for analysing causal relationships was inverse variance-weighted (IVW) analysis, and the MR results were validated through various sensitivity analyses.ResultsMR analysis revealed that 28 gut microbiome taxa and 75 immune cell types were significantly associated with prostate diseases. Furthermore, reverse MR analysis did not support a causal relationship between prostate diseases and the intestinal microbiota or immune cells. Finally, the results of the mediation analysis indicated that Secreting Treg % CD4 Treg, Activated & resting Treg % CD4 Treg, and Mo MDSC AC inhibited the role of the class Mollicutes in reducing the risk of PCa. In prostatitis, CD8+ T cells on EM CD8br hinder the increased risk associated with the genus Eubacterium nodatum group. Interestingly, in BPH, CD28- CD25++CD8br AC and CD16-CD56 on HLA DR+ NK promoted the role of the genus Dorea in reducing the risk of BPH.ConclusionThis study highlights the complex relationships among the gut microbiota, immune cells and prostate diseases. The involvement of the gut microbiota in regulating immune cells to impact prostate diseases could provide novel methods and concepts for its therapy and management.