Tongxie Yaofang attenuates ulcerative colitis by modulating gut microbiota and IL-10RA/NF-κB-mediated macrophage polarization.

BACKGROUND

Tongxie Yaofang (TXYF), a traditional Chinese herbal formula, has shown therapeutic potential in gastrointestinal disorders. However, its mechanism in ulcerative colitis (UC) remains unclear. This study provides new insights into immune-microbiota crosstalk as a key mechanism driving the protective effects of TXYF.

METHODS

A DSS-induced colitis mouse model was used to evaluate TXYF's efficacy. Gut microbiota was profiled by 16S rRNA sequencing, while transcriptomics and network pharmacology identified core pathways. In vivo and in vitro assays examined immune regulation and epithelial barrier function. A THP-1/Caco-2 co-culture system explored IL-10RA-dependent immune-epithelial crosstalk, and fecal microbiota transplantation (FMT) tested the functional role of microbial remodeling.

RESULTS

TXYF alleviated colitis symptoms, improved colon histology, and reduced pro-inflammatory cytokines. It reshaped gut microbiota by enriching SCFA-producing beneficial taxa and suppressing pathogenic bacteria. Transcriptomic analyses identified IL-10RA/NF-κB as a novel regulatory axis, and TXYF enhanced IL-10RA expression, inhibited NF-κB activation, and promoted M2 macrophage polarization. The co-culture model revealed IL-10RA-dependent macrophage-epithelial signaling that strengthened tight junction integrity. Importantly, FMT from TXYF-treated donors yielded these therapeutic benefits, reinforcing the evidence for microbiota-driven causality.

CONCLUSION

This study is the first to identify IL-10RA/NF-κB as a key immunoregulatory pathway of TXYF, uncover IL-10RA-dependent immune-epithelial communication, and validate gut microbiota as a functional mediator through FMT. Collectively, these findings demonstrate the innovative potential of TXYF as a multi-target herbal therapy for UC.