Abstract

Chronic non-bacterial prostatitis (CNP) is one of the most prevalent diseases in human males worldwide. In 2005, the prostate-gut axis was first proposed to indicate the close relationship between the prostate and the intestine. This study investigated CNP-induced changes of the gut microbiota, gene expression and DNA methylation in a rat model by using multi-omics analysis. Firstly, 16S rDNA sequencing presented an altered structure of the microbiota in cecum of CNP rats. Then, transcriptomic analysis revealed that the expression of 185 genes in intestinal epithelium was significantly changed by CNP. These changes can participate in the immune system, digestive system, metabolic process, etc. Finally, methylC-capture sequencing (MCC-Seq) found 73,232 differentially methylated sites (DMSs) in the DNA of intestinal epithelium between control and CNP rats. A combined analysis of methylomics and transcriptomics suggested an epigenetic mechanism for CNP-induced differential expression genes correlated with intestinal barrier function, immunity, metabolism, enteric infectious disease, etc. More importantly, the transcriptomic, methylomic and gut microbial changes were highly correlated with multiple processes including intestinal immunity, metabolism and epithelial barrier function. In this study, disrupted homeostasis in the gut microbiota, gene expression and DNA methylation were reported in CNP, which supports the existence of the gut-prostate axis.

Highlights

  • Chronic non-bacterial prostatitis (CNP) is a common urinary disease, especially occurring in men below the age of 50

  • By 16S rDNA sequencing, 757 and 758 operational taxonomic units (OTUs) were generated for the control (CTL) and CNP groups, respectively, and 754 OTUs were shared by them. Genome alignment found these OTUs belonged to 168 genera, which were all shared by the CTL and CNP groups

  • We investigated the effects of CNP on DNA methylation of intestinal epithelium by MethylC-Capture Sequencing (MCC-Seq)

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Summary

Introduction

Chronic non-bacterial prostatitis (CNP) is a common urinary disease, especially occurring in men below the age of 50. It is estimated that approximately 50% of all men suffer from prostatitislike symptoms in their lives, and CNP accounts for 25% of all visits to urological clinics worldwide (Khan et al, 2017). Due to the heterogeneity of CNP, these management strategies are often ineffective, and this condition remains problematic to treat. Uric acid level, inflammation, autoimmunity or neuro-muscular mechanisms are all thought to be the etiologies, the pathogenesis of CNP is still controversial (Khan et al, 2017). Providing a clear understanding of the pathogenic basis of CNP, as well as its complications, is critical for treatment and healthcare of this complex disease

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