Abstract:

Objective

To investigate the pathogenesis of chronic pancreatitis (CP), validate the relationship between CP, gut microbiota,and immune-inflammatory factors,and provide more comprehensive data support for the study of CP etiology.

Methods

Part 1:Patients admitted to the Second Affiliated Hospital of Baotou Medical College from January 2023 to December 2024 were recruited and divided into an experimental group (CP patients) and a control group (healthy individuals) based on predefined criteria.Fecal samples were collected for 16S rRNA sequencing, and serum levels of inflammatory factors, including IL-6,IL-8,IL-1β, tumor necrosis factor-α (TNF-α),and nuclear factor-κB p65 (NF-κB p65), were measured using ELISA. Differences in gut microbiota and inflammatory factors between CP patients and healthy controls were analyzed. Part 2: A dibutyltin dichloride (DBTC)-induced CP rat model was established, with rats divided into an experimental group (CP model) and a control group (blank control).DBTC was administered at high (1.6 mg·kg ^-1) and low (0.8 mg·kg ^-1) concentrations, respectively.Fecal and blood samples were collected for testing.

Results

Significant differences in gut microbiota were observed between CP patients and healthy controls, characterized by a decrease in beneficial bacteria and an increase in pathogenic bacteria.Serum levels of IL-6 (P <0.05), IL-8 (P <0.01),IL-1β (P <0.001),and NF-κB p65 (P <0.01) were higher in the CP group than in the control group,whereas TNF-α (P <0.001) was higher in the control group. Similarly,fecal test results in the CP rat model were consistent with human findings, and blood levels of NF-κB p65,IL-1β,IL-8,and TNF-α were significantly higher in the experimental group than in the control group (P <0.0001),with IL-6 (P <0.01) also elevated.

Conclusion

The study demonstrates that chronic pancreatitis is associated with gut microbiota dysbiosis and elevated immune-inflammatory factors. Furthermore,it proposes the hypothesis that gut microbiota regulates CP through the IL-1β/NF-κB p65 signaling pathway. Additionally,the high-dose DBTC-induced CP rat model was found to be more stable,providing a basis for future research.

Key words: Chronic pancreatitis, Gut microbiota, IL-1β, NF-κB