Luohuazizhu Granules Alleviate Symptoms of Ulcerative Colitis via Changes in Bile Acid Metabolism and Gut Microbiota

Introduction: Luohuazizhu granules (LHZZG) are made of Callicarpa nudiflora Hook. (CN), which is used to treat ulcerative colitis (UC). The anti-inflammatory effects of CN on UC have been previously reported. However, the biological effects of LHZZG on bile acids (BAs) in UC and the underlying mechanisms remain unexplored. Methods: Integrated metabolomics were used to explore the regulatory mechanisms of LHZZG for BA metabolism in UC mice. Both 16S rDNA sequencing and flow cytometry analyses were combined to comprehensively assess gut microbiota (GM) and immune responses. Results: Twenty-five differential biomarkers were identified in the untargeted metabolomic analysis, most of which were correlated with BA metabolism. UC signs were significantly alleviated after LHZZG treatment. The targeted metabolomics analysis revealed BA metabolic disorders to be significantly improved following LHZZG treatment. Additionally, the imbalances in the GM and immune cells related to BA metabolism were restored. Discussion: This study not only confirmed significant dose-dependent protective effects of LHZZG in UC mice, but also performed the first investigation into the underlying mechanisms related to BA metabolism and immune function. Nevertheless, the limitations precluded a definitive mechanistic explanation for the observed changes. Consequently, in-depth mechanistic investigations will be prioritized in subsequent research to experimentally validate this hypothesis. Conclusion: BAs could serve as biomarkers for evaluating the therapeutic effects of LHZZG on UC. This study has provided the first detailed explanation of the mechanism underlying the effects of LHZZG from a BA metabolic perspective, providing a foundation for their clinical application in UC.