AccScience Publishing / Bladder / Online First / DOI: 10.14440/bladder.2024.0060
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RESEARCH ARTICLE

Pentosan polysulfate alleviates interstitial cystitis/bladder pain syndrome by modulating bile acid metabolism and activating the TGR5 receptor through gut microbiota regulation

Zhangrui Zhu1† ,  Yuexuan Zhu1† ,  Qi Sun1† ,  Jingwen Xue1 ,  Ming Xie1 ,  Yao Yu1 ,  Benlin Wang1 ,  Wentai Shangguan1 ,  Zhengyuan Feng1 ,  Peng Wu1*
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1 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
Bladder, e21200036 https://doi.org/10.14440/bladder.2024.0060
Submitted: 12 November 2024 | Revised: 31 December 2024 | Accepted: 11 February 2025 | Published: 24 March 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Background: The disrupted gut microbiome has been found to be implicated in the development of interstitial cystitis/bladder pain syndrome (IC/BPS). Pentosan polysulfate (PPS) is an oral medication used for treating IC/BPS, acting as both an anti-inflammatory agent and a bladder barrier protector. However, the precise mechanisms by which the PPS-mediated modulation of the gut microbiome alleviates IC/BPS are not fully understood. Objective: This study aimed to identify the key gut microbiota species and metabolites involved in PPS’s protective effects against IC/BPS. Methods: We employed a multifaceted approach, including 16S rDNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation, to validate the dependency of PPS’s protective effects on the gut microbiome. Furthermore, we performed a comprehensive metabolomic profiling using non-targeted metabolomics and liquid chromatography-tandem mass spectrometry. Results: PPS significantly elevated the abundance of the xylan-degrading bacteria, Eubacterium xylanophilum group, which, through its interaction with the gut microbiome, markedly reduced inflammation and barrier damage induced by cyclophosphamide in IC/BPS. In addition, PPS significantly increased the level of ursodeoxycholic acid (UDCA), a secondary bile acid, demonstrating a strong correlation with the abundance of the E. xylanophilum group. Ex vivo supplementation with UDCA mitigated lipopolysaccharide-induced inflammation and barrier disruption in SV-HUC-1 cells by activating the TGR5 receptor. Conclusion: PPS exerts its protective effects against IC/BPS by modulating the gut microbiome and its metabolites.

Keywords
Interstitial cystitis/bladder pain syndrome
Pentosan polysulfate
Cyclophosphamide
Ursodeoxycholic acid
Bladder barrier
Gut microbiota
Funding
This work was supported by the National Natural Science Foundation of China (Grant number: 82370782).
Conflict of interest
The authors declare no conflicts of interest.
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Bladder, Electronic ISSN: 2327-2120 Print ISSN: TBA, Published by POL Scientific
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