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

## TL;DR

Pentosan polysulfate helps treat bladder pain syndrome by changing gut bacteria and bile acids, which reduce inflammation.

## Contribution

The study identifies how PPS modulates gut microbiota and bile acid metabolism to alleviate IC/BPS.

## Key findings

- PPS increases Eubacterium xylanophilum group, reducing inflammation and bladder damage.
- PPS raises ursodeoxycholic acid levels, which activate TGR5 receptor and reduce inflammation.
- Gut microbiome modulation is essential for PPS's protective effects against IC/BPS.

## Abstract

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.

This study aimed to identify the key gut microbiota species and metabolites involved in PPS’s protective effects against IC/BPS.

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.

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.

PPS exerts its protective effects against IC/BPS by modulating the gut microbiome and its metabolites.