Alcohol intake exacerbates experimental autoimmune prostatitis through gut microbiota driving cholesterol biosynthesis-mediated Th17 differentiation.

Autor:	Du HX; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China., Yue SY; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China., Niu D; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China., Liu XH; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China., Li WY; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China., Wang X; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China., Chen J; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China., Hu DK; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China., Zhang LG; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China., Guan Y; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China., Ji DX; Clinical Medical College, Anhui Medical University, Hefei, Anhui, PR China., Chen XG; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China. Electronic address: cxg7866186@126.com., Zhang L; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China. Electronic address: lzhang@ahmu.edu.cn., Liang CZ; Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, PR China; Institute of Urology, Anhui Medical University, Hefei, Anhui, PR China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, PR China. Electronic address: ayfymw@163.com.
Jazyk:	angličtina
Zdroj:	International immunopharmacology [Int Immunopharmacol] 2024 Sep 30; Vol. 139, pp. 112669. Date of Electronic Publication: 2024 Jul 18.
DOI:	10.1016/j.intimp.2024.112669
Abstrakt:	Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is very common worldwide, and alcohol consumption is a notable contributing factor. Researches have shown that gut microbiota can be influenced by alcohol consumption and is an important mediator in regulating Th17 cell immunity. However, it is still unclear the exact mechanism by which alcohol exacerbates the CP/CPPS and the role of gut microbiota in this process. Method: We first constructed the most-commonly used animal model for CP/CPPS, the experimental autoimmune prostatitis (EAP) model, through immunoassay. Based on this, mice were divided into EAP group and alcohol-consuming EAP group. By 16S rRNA sequencing and non-targeted metabolomics analysis, differential gut microbiota and their metabolites between the two groups were identified. Subsequently, metabolomics detection targeting cholesterols was carried out to identify the exact difference in cholesterol. Furthermore, multiple methods such as flow cytometry and immunohistochemistry were used to detect the differentiation status of Th17 cells and severity of prostatitis treated with 27-hydroxycholesterol (the differential cholesterol) and its upstream regulatory factor-sterol regulatory element-binding protein 2 (SREBP2). Lastly, fecal transplantation was conducted to preliminary study on whether alcohol intake exacerbates EAP in immune receptor mice. Results: Alcohol intake increased the proportion of Th17 cells and levels of related inflammatory factors. It also led to an altered gut bacterial richness and increased gut permeability. Further metabolomic analysis showed that there were significant differences in a variety of metabolites between EAP and alcohol-fed EAP mice. Metabolic pathway enrichment analysis showed that the pathways related to cholesterol synthesis and metabolism were significantly enriched, which was subsequently confirmed by detecting the expression of metabolic enzymes. By targeting cholesterol synthesis, 27-hydroxycholesterol was significantly increased in alcohol-fed EAP mice. Subsequent mechanistic research showed that supplementation with 27-hydroxycholesterol could aggravate EAP and promote Th17 cell differentiation both in vivo and in vitro, which is regulated by SREBP2. In addition, we observed that fecal transplantation from mice with alcohol intake aggravated EAP in immunized recipient mice fed a normal diet. Conclusion: Our study is the first to show that alcohol intake promotes Th17 cell differentiation and exacerbates EAP through microbiota-derived cholesterol biosynthesis. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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