# Renshen-Baidu-San restores epithelial–immune crosstalk and drives type 2 immune repair in ulcerative colitis: an integrated multi-omics study

## TL;DR

This study explores how a traditional Chinese herbal formula, Renshen-Baidu-San, helps treat ulcerative colitis by restoring immune and epithelial communication and promoting tissue repair.

## Contribution

The study reveals novel mechanisms by which Renshen-Baidu-San modulates metabolic and immune pathways to drive type 2 immune repair in ulcerative colitis.

## Key findings

- BDS modulates steroid and lipid metabolites, affecting hormone biosynthesis and lipid pathways.
- BDS restores epithelial-immune communication and promotes mucosal repair via type 2 immune responses.
- Colon organoid experiments confirmed structural recovery and increased Tuft cells with reduced inflammation.

## Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa characterized by recurrent flares and difficulty achieving sustained remission. Renshen-Baidu-San (BDS), a classical Chinese herbal prescription, has shown promising clinical benefit in relieving UC symptoms, but its underlying therapeutic mechanisms remain insufficiently defined. This study aimed to elucidate the multiple biological mechanisms underlying the therapeutic effects of BDS in UC.

We utilized an integrated multi-omics and experimental approach, combining serum metabolomics, pharmacological network analysis, molecular docking, and single-cell RNA sequencing in a DSS-induced UC mouse model, supplemented by colon organoid experiments. Key findings were validated using histopathology, immunohistochemistry, immunofluorescence, quantitative RT-PCR, ELISA, and flow cytometry.

Serum metabolomics demonstrated that BDS modulates steroid- and lipid-derived metabolites, thereby influencing steroid hormone biosynthesis, bile acid turnover, and lipid pathways including arachidonic acid and linoleic acid metabolism. Network pharmacology based on serum-detected components further highlighted BDS’s regulatory effects on inflammatory signaling and cellular proliferation, while molecular docking identified stable and favorable protein-ligand interactions. Single-cell transcriptomics revealed that BDS corrected UC-induced epithelial–immune dysregulation, with Tuft and T-1 cell subclusters emerging as key responders through coordinated suppression of NF-κB–driven TNF-α signaling; ligand–receptor analysis indicated restoration of epithelial–immune communication. Colon organoid experiments corroborated mucosal repair, crypt structural recovery, Tuft cell expansion, and a shift toward a tissue-restorative type 2 immune profile, characterized by elevated IL-4 and IL-25 and reduced IL-13.

Our findings indicate that BDS treatment in DSS-induced colitis is accompanied by alterations in metabolic pathways, epithelial-immune communication, and cell-type-specific transcriptional programs, which may be relevant to type 2 immune–mediated mucosal repair processes.