Frontiers in Immunology (Jul 2022)
Gut Microflora Modulates Th17/Treg Cell Differentiation in Experimental Autoimmune Prostatitis via the Short-Chain Fatty Acid Propionate
- He-Xi Du,
- He-Xi Du,
- He-Xi Du,
- Shao-Yu Yue,
- Shao-Yu Yue,
- Shao-Yu Yue,
- Di Niu,
- Di Niu,
- Di Niu,
- Chang Liu,
- Chang Liu,
- Chang Liu,
- Li-Gang Zhang,
- Li-Gang Zhang,
- Li-Gang Zhang,
- Jing Chen,
- Jing Chen,
- Jing Chen,
- Yang Chen,
- Yang Chen,
- Yang Chen,
- Yu Guan,
- Yu Guan,
- Yu Guan,
- Xiao-Liang Hua,
- Xiao-Liang Hua,
- Xiao-Liang Hua,
- Chun Li,
- Chun Li,
- Chun Li,
- Chun Li,
- Xian-Guo Chen,
- Xian-Guo Chen,
- Xian-Guo Chen,
- Li Zhang,
- Li Zhang,
- Li Zhang,
- Chao-Zhao Liang,
- Chao-Zhao Liang,
- Chao-Zhao Liang
Affiliations
- He-Xi Du
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- He-Xi Du
- Institute of Urology, Anhui Medical University, Hefei, China
- He-Xi Du
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- Shao-Yu Yue
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Shao-Yu Yue
- Institute of Urology, Anhui Medical University, Hefei, China
- Shao-Yu Yue
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- Di Niu
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Di Niu
- Institute of Urology, Anhui Medical University, Hefei, China
- Di Niu
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- Chang Liu
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Chang Liu
- Institute of Urology, Anhui Medical University, Hefei, China
- Chang Liu
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- Li-Gang Zhang
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Li-Gang Zhang
- Institute of Urology, Anhui Medical University, Hefei, China
- Li-Gang Zhang
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- Jing Chen
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Jing Chen
- Institute of Urology, Anhui Medical University, Hefei, China
- Jing Chen
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- Yang Chen
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Yang Chen
- Institute of Urology, Anhui Medical University, Hefei, China
- Yang Chen
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- Yu Guan
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Yu Guan
- Institute of Urology, Anhui Medical University, Hefei, China
- Yu Guan
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- Xiao-Liang Hua
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Xiao-Liang Hua
- Institute of Urology, Anhui Medical University, Hefei, China
- Xiao-Liang Hua
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- Chun Li
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Chun Li
- Institute of Urology, Anhui Medical University, Hefei, China
- Chun Li
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- Chun Li
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Xian-Guo Chen
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Xian-Guo Chen
- Institute of Urology, Anhui Medical University, Hefei, China
- Xian-Guo Chen
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- Li Zhang
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Li Zhang
- Institute of Urology, Anhui Medical University, Hefei, China
- Li Zhang
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- Chao-Zhao Liang
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- Chao-Zhao Liang
- Institute of Urology, Anhui Medical University, Hefei, China
- Chao-Zhao Liang
- Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China
- DOI
- https://doi.org/10.3389/fimmu.2022.915218
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords