GLYCYROL ACTIVATES AUTOPHAGY TO PROTECT 5-FLUOROURACIL INDUCED COLON INJURY IN MICE BY REGULATING GUT MICROBIOTA AND GUT MICROBIOTA DERIVED METABOLITES
Objective To explore whether glycyrol(GC)can protect against colon damage by regulating gut microbiota and metabolite to activate autophagy.Methods Male Balb/C mice(6 weeks old)were adaptively fed for 1 week and randomly divided into control group(N):gavage of physiological saline for 14 days+intraperitoneal injection of physiological saline for 3 days;Colonic injury model group(5-FU):gavage of physiological saline for 14 days+intraperitoneal injection of 5-fluorouracil(5-FU,100 mg/kg)for 3 days;GC intervention group(GC):gavage of GC(20 mg/kg)for 14 days+intraperitoneal injection of physiological saline for 3 days;GC+5-FU group:gavage of GC(20 mg/kg)for 14 days+intraperitoneal injection of 5-FU(100 mg/kg)for 3 days;Antibiotic group(AB):gavage of antibiotics(200 μl)for 14 days+intraperitoneal injection of physiological saline for 3 days;GC+5-FU+AB group:Administer antibiotics(200 μl)by gavage for 14 days,GC(20 mg/kg)by gavage for 14 days,and intraperitoneal injection of 5-FU(100 mg/kg)for 3 days,with 8 animals in each group.HE staining and Western blot analysis were used to determine the protective effect of GC on colon injury in mice.High-throughput 16S rDNA sequencing and metabolomics were conducted to investigate the effects of GC on gut microbiota structure,gut metabolites,and colon autophagy levels in mice colon damaged mice;Using correlation analysis to elucidate the mechanism by which GC protects against colon injury by regulating gut microbiota and its metabolites to activate autophagy.Results Compared with the 5-FU group,GC intervention can significantly improve the body weight,food intake,and colon superoxide dismutase(SOD)and catalase(CAT)activity.Significantly reduces colon interleukin 1 beta(IL-1β),Interleukin 6(IL-6)and tumor necrosis factor alpha(TNF-α)level in mice,and significantly reduce damage to colon tissue.GC can also improve the structure of gut microbiota,upregulate the abundance of Firmicutes and Campylobacter,downregulate the abundance of Proteobacteria and Bacteroidetes,restore abnormal changes in Bacteroidetes,Spirochetes,and Prevotellaceae.GC significantly downregulated the levels of six gut microbiota metabolites,including cholecalciferol,and significantly upregulated the levels of eight gut microbiota metabolites,including TNK.The correlation analysis results show that there is a correlation between various gut microbiota metabolites and the level of autophagy in the mouse colon.Conclusion GC activates autophagy to protect colon injury,which is related to regulating gut microbiota and its metabolites.[ACTA NUTRIMENTA SINICA,2024,46(4):372-382]
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