# Abnormal Gut Microbiota is Associated with Depressive-like Behavior in the Rat Model of Autoimmune Prostatitis

## TL;DR

This study shows that gut microbiota imbalances are linked to depressive-like behavior in rats with autoimmune prostatitis.

## Contribution

The study identifies specific gut microbiota changes and metabolic pathways associated with prostatitis and depression in a rat model.

## Key findings

- EAP + CUMS rats showed disordered gut microbiota abundance, uniformity, and composition.
- Over 60 gut microbial metabolic pathways were predicted to be disordered in EAP + CUMS rats.
- Metabolomics profiling revealed significant differences in specific pathways linked to several bacterial genera.

## Abstract

Many patients with chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) also experience depression, although the pathogenesis was unclear. Some studies have shown that gut microbiota disorder might be related to both prostatitis and depression. Therefore, we investigated the alteration of the gut microbiota in autoimmune CP/CPPS complicated with depression in a rat model. The rat model of autoimmune CP with comorbid depressive-like behavior was constructed by experimental autoimmune prostatitis (EAP) and chronic unpredictable mild stress (CUMS). Then, enzyme linked immunosorbent assay (ELISA) was performed to determine the concentration of inflammatory cytokines. The depression-like behaviors in rats were also detected using the open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT). The composition of the gut microbiota and the microbial profile in rats were measured by bioinformatics analysis of the 16S rRNA gene sequence. The level of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), and depression-like behavior in rats showed that the CP/CPPS complicated with depression model was established successfully. The results of the 16S rRNA sequence analysis showed disordered abundance, uniformity, and composition of gut microbiota in EAP + CUMS rats. Over 60 gut microbial metabolic pathways were predicted to be disordered among the four groups of rats. Additionally, metabolomics profiling indicated significant differences in EAP + CUMS rats compared to other groups, including reduced PWY-922, PWY-5198 and PWY-7159, and increased PWY0-321 and PWY-6629, which were predicted to be altered by Lactobacillus, Shigella, Blautia, Clostridiales, Comamonadaceae and Rhodospirillales. Our results have shown that gut microbiota disorders are associated with depressive-like behavior in experimental prostatitis. Our findings concerning gut microbiota provide new insights in understanding prostatitis-associated depression.

The online version contains supplementary material available at 10.1007/s12010-025-05294-1.