Pentosan polysulfate alleviates cyclophosphamide-induced interstitial cystitis/bladder pain syndrome in mice by modulating gut microbiota and bile acid metabolism.
10.12122/j.issn.1673-4254.2025.06.16
- Author:
Yuexuan ZHU
1
;
Zhangrui ZHU
1
;
Peng WU
1
Author Information
1. Department of Urology, Nanfang Hospital Southern Medical University, Guangzhou 510515, China.
- Publication Type:Journal Article
- Keywords:
bile acids;
cyclophosphamide;
gut microbiota;
interstitial cystitis/bladder pain syndrome;
pentosan polysulfate
- MeSH:
Animals;
Cystitis, Interstitial/drug therapy*;
Gastrointestinal Microbiome/drug effects*;
Pentosan Sulfuric Polyester/therapeutic use*;
Cyclophosphamide/adverse effects*;
Mice, Inbred C57BL;
Female;
Mice;
Bile Acids and Salts/metabolism*;
Urinary Bladder;
Fecal Microbiota Transplantation;
Humans
- From:
Journal of Southern Medical University
2025;45(6):1270-1279
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the therapeutic efficacy and mechanism of pentosan polysulfate (PPS) for cyclophosphamide (CYP)-induced interstitial cystitis/bladder pain syndrome (IC/BPS) in mice.
METHODS:Female C57BL/6 mice (6-8 weeks old) were randomized into control group, PPS treatment (25 mg/kg via gavage for 3 weeks) group, CYP treatment (3 separate intraperitoneal injections at 50 mg/kg in week 4), and CYP+PPS treatment group. Gut microbiota alterations of the mice were analyzed using 16S rDNA sequencing and non-targeted metabolomics. Fecal microbiota transplantation (FMT) was performed in CYP-treated recipient mice and those treated with both CYP and PPS. In the in vitro experiment, LPS-stimulated human bladder epithelial cells (SV-HUC-1) were used to assess the effects of deoxycholic acid (DCA) and TGR5 signaling inhibitor SBI-115 on barrier functions of bladder epithelial cells.
RESULTS:PPS treatment significantly improved the mechanical pain thresholds, restored the urodynamic parameters, and attenuated bladder inflammation and barrier dysfunction in CYP-treated mice. Mechanistically, PPS enriched the abundance of Eubacterium xylanophilum and increased DCA levels in the intestines of CYP-treated mice. FMT experiments confirmed microbiota-dependent therapeutic effects of PPS, shown by reduced bladder pathology in the recipient mice treated with both CYP and PPS. In SV-HUC-1 cells, DCA obviously alleviated LPS-induced inflammation and barrier disruption, and treatment with SBI-115 abolished these protective effects of DCA.
CONCLUSIONS:PPS ameliorates IC/BPS in mice by remodeling gut microbiota to enhance DCA production and activate TGR5 signaling, suggesting a novel microbiota-bile acid-TGR5 axis that mediates the therapeutic effect of PPS and a therapeutic strategy for IC/BPS by targeting gut-bladder crosstalk.
