High-Throughput Sequencing Reveals ChaiHu ShuYi Formula AlleviatesChronic Pancreatitis by Remodeling Gut Microbiota in Mice

Introduction: Chronic pancreatitis (CP), characterized by progressive pancreatic fibrosis and irreversible tissue damage, lacks definitive therapies. Chaihu Shuyi Formula (CHSYF), a traditional Chinese medicine containing constituents with anti-inflammatory and anti- fibrotic phytochemicals, demonstrates therapeutic potential for CP; however, the therapeutic effects and mechanisms underlying its modulation of the microbiota remain incompletely characterized. Methods: This study evaluated the therapeutic effects of CHSYF on caerulein-induced CP in mice through histopathological analysis and high-throughput 16S rRNA sequencing of gut microbiota. Results: CHSYF treatment significantly alleviated inflammatory symptoms in CP mice, as evidenced by increased body and pancreatic weights, reduced levels of ALT, AST, IL-6, and TNF- α, and decreased pathological damage, including fibrotic lesions in pancreatic tissues. Analysis of the gut microbiota revealed that CHSYF altered the microbial structure, reduced species richness, and improved gut microbiota imbalance in CP mice. Treatment with CHSYF led to significant decreases in Odoribacter, Faecalibaculum, and Alloprevotella, and a shift in the dominant bacterial communities toward norankf_Oscillospiraceae, Parabacteroides, Alistipes, and Muribaculum. The gut microbiota of CHSYF-treated mice primarily participate in the endocannabinoid and lysine metabolic pathways. Conversely, the gut microbiota of mice with CP was more involved in pathways such as apelin signaling and calcium signaling. Conclusion: CHSYF modulated the gut microbiota in mice with caerulein-induced CP, thereby attenuating pancreatic injury. This study provides novel insights into the application of CHSYF for the treatment of CP.