Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a very common urological disorder and has been gradually regarded as an immune-mediated disease. Multiple studies have indicated that the gut microflora plays a pivotal part in immune homeostasis and autoimmune disorder development. However, whether the gut microflora affects the CP/CPPS, and the underlying mechanism behind them remain unclear. Here, we built an experimental autoimmune prostatitis (EAP) mouse model by subcutaneous immunity and identified that its Th17/Treg frequency was imbalanced. Using fecal 16s rRNA sequencing and untargeted/targeted metabolomics, we discovered that the diversity and relative abundance of gut microflora and their metabolites were obviously different between the control and the EAP group. Propionic acid, a kind of short-chain fatty acid (SCFA), was decreased in EAP mice compared to that in controls, and supplementation with propionic acid reduced susceptibility to EAP and corrected the imbalance of Th17/Treg cell differentiation in vivo and in vitro. Furthermore, SCFA receptor G-protein-coupled receptor 43 and intracellular histone deacetylase 6 regulated by propionic acid in Th17 and Treg cells were also evaluated. Lastly, we observed that fecal transplantation from EAP mice induced the decrease of Treg cell frequency in recipient mice. Our data showed that gut dysbiosis contributed to a Th17/Treg differentiation imbalance in EAP via the decrease of metabolite propionic acid and provided valuable immunological groundwork for further intervention in immunologic derangement of CP/CPPS by targeting propionic acid.

Myeloid-derived suppressor cells (MDSCs) expand when the body undergoes inflammatory diseases and chronic diseases. However, its role in intervertebral disc degeneration remains unclear. The present study aimed to characterize specific subsets of MDSCs as potential indicators of disease progression in patients with lumbar disc herniation (LDH). The Gene Expression Omnibus (GEO) database was used to analyze the changes in granulocyte MDSCs (G-MDSCs). Peripheral blood samples were collected from 40 patients with LDH and 15 healthy controls, and flow cytometry was used to characterize different subsets of MDSCs. All subjects underwent lumbar spine magnetic resonance imaging. Then, t-distributed stochastic neighborhood embedding and FlowSOM were used to analyze the data obtained by CytoFlex. The correlation between circulating MDSCs and the clinicopathological stage of LDH was then further analyzed. The GEO database predicted that G-MDSCs were highly expressed in patients with LDH. The frequency of circulating G-MDSCs increased with Pfirrmann stage III and IV, while the percentage of mononuclear MDSCs (M-MDSCs) only increased. Patient age and sex did not correlate with the frequency of circulating G-MDSCs and M-MDSCs. The results of the computer algorithm analysis were consistent with those of our manual gating. The present study showed that the occurrence of LDH led to changes in the MDSC subpopulation in the circulating peripheral blood of patients, and the frequency of circulating G-MDSCs in patients with clinical stage III and IV LDH increased with the degree of degeneration. The determination of G-MDSCs can be used as an auxiliary examination item for LDH.