Multi-Omics Analysis Reveals Changes in the Intestinal Microbiome, Transcriptome, and Methylome in a Rat Model of Chronic Non-bacterial Prostatitis: Indications for the Existence of the Gut-Prostate Axis

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.

Gut Microflora Modulates Th17/Treg Cell Differentiation in Experimental Autoimmune Prostatitis via the Short-Chain Fatty Acid Propionate

“…Further probing revealed that EAP mice have obviously decreased contents of SCFA propionate in both feces and serum, and propionic acid supplementation attenuated EAP severity and restored its Th17/Treg balance, which was possibly linked to the GPR43 activation and HDAC6 inhibition. Our research broadens the horizons of the correlation between gut microflora and extra-intestinal organs or immune cells and provided new lines of evidence for the previously proposed concept of the “gut–prostate” axis ( 33 ).…”

“…Further probing revealed that EAP mice have obviously decreased contents of SCFA propionate in both feces and serum, and propionic acid supplementation attenuated EAP severity and restored its Th17/Treg balance, which was possibly linked to the GPR43 activation and HDAC6 inhibition. Our research broadens the horizons of the correlation between gut microflora and extra-intestinal organs or immune cells and provided new lines of evidence for the previously proposed concept of the "gut-prostate" axis (33). It has been now becoming widely accepted that the large amounts of commensal gut bacteria not only are restricted to regulate the intestinal mucosal immunity and maintain the intestinal homeostasis, but also exert systemic effects on immune cells in extra-intestinal organs or tissues (34).…”

“…Shoskes et al (16) first found that patients with CPPS have markedly less gut microbiome diversity in clusters that is different from controls. Then, Liu et al (33) took a big step forward by suggesting an epigenetic mechanism for chronic nonbacterial prostatitis that is correlated with gut microbiota, immunity, and metabolism using multi-omics analysis. Since Th17 and Treg cells are the key immune cells that may regulate the development of CP/CPPS under the condition of when Th17 cells are activated and Treg cells are inhibited (37), it is necessary to demonstrate the gut dysbiosis and Th17/Treg cell immune imbalance in EAP and uncover whether there was an objective arrived-at connection between them.…”

Association between Antibiotic Use and Subsequent Risk of Prostate Cancer: A Retrospective Cohort Study in South Korea

“…Antibiotics may cause a change in bacterial diversity that leads to dysbiosis [21,22]. In this regard, recent research has established a "gutprostate axis" in the association between gut microbiota and prostate health, including prostate cancer [23][24][25]. Insulin-like growth factor 1 (IGF-1), affected by the gut microbiome, has been linked to prostate cancer, which acts as an aggravating factor [24].…”

Prostate and gut: Any relationship? A narrative review on the available evidence and putative mechanisms

“…51 Noteworthy, currently available conventional analgesics (such as acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids) and even other, more evidence-based pharmacological options (including anti-spasmodics, tricyclic antidepressants, and other neuromodulatory therapies), are frequently ineffective and/or associated with significant side effects for patients with interstitial cystitis, CNP, and IBS, thus are difficult to treat. 42,52 Potentially, one of such could be represented by microbiome modification. Until recently, it was believed that human urogenital tract is sterile.…”