普拉梭菌上清增强肝纤维化小鼠肠道屏障功能抑制肝脏炎症

Objective To investigate the effects of the culture supernatant of Faecalibacterium prausnitzii(F. prausnitzii)on intestinal barrier function and liver fibrosis progression in mice. Methods A total of 24 male C57BL/6 mice were randomly assigned to three groups: normal control group(Control), liver fibrosis model group(Model), and model mice + F. prausnitzii supernatant group(Model+S). Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride in both the Model group and the Model+S group over a period of 10 weeks. Following a 2-week modeling period, the mice in the Model+S group were subjected to an 8-week treatment with bacterial supernatant. The colon and liver were analyzed for pathological morphology using HE staining. Additionally, impairment of intestinal barrier function was assessed by periodic acid schiff staining, ELISA, and fluorescein isothiocyanate-dextran(FITC-Dextran)fluorescent probe. Changes in the gut microbiota structure were analyzed with 16S rDNA sequencing. The degree of liver fibrosis was assessed using sirius red staining, and the expression levels of markers associated with intestinal barrier function, liver fibrosis, and inflammation were measured using qPCR and ELISA. Results Compared with the Model group, the severity of intestinal damage and the expressions of pro-inflammatory factors in the Model+S group were decreased. Additionally, there was a significant increase in the expressions of multiple genes related to intestinal barrier function, as well as a decrease in the concentration of FITC-Dextran in peripheral blood and lipopolysaccharide in the liver(all P<0.05), and there was an improvement in the composition of the gut microbiota. Furthermore, while the liver function and extent of liver fibrosis in the Model+S group did not show any significant differences compared to the Model group, there was a noticeable decrease in the infiltration of inflammatory cells within the liver. Additionally, the expressions of pro-inflammatory factors such as Tlr4, Il-6 and Tnf-α, and the concentration of IL-6 in the liver was significantly decreased(all P<0.05). Conclusion The F. prausnitzii supernatant exhibits the potential to enhance intestinal barrier function and rectify gut microbiota imbalance in mice with liver fibrosis, thus reducing hepatic inflammation. However, it does not exert any significant effect on the progression of liver fibrosis.