IDDF2024-ABS-0317 Mechanistic study of naringenin to alleviate DSS-induced IBD as revealed by 16s rDNA-based and metabolomics analysis

Background

Inflammatory bowel disease (IBD) poses a heavy burden on global health, and since its pathogenesis has not been elucidated and there is still no effective treatment, the development of new drugs is urgent. Naringenin has considerable potential in the treatment of IBD, but the mechanism of its action remains unknown. The present study aimed to validate the effect of naringenin in the treatment of IBD and investigate its mechanism of action.

Methods

Male C57BL/6j mice at 6-8 weeks of age were treated with naringin by gavage after constructing a mouse IBD model by drinking 4% dextrose sodium sulfate (DSS) sterile water for one week. The effects of naringin on IBD were verified by evaluating body weight changes, disease activity index, colon length and weight, histological scores, cytokine levels, and antioxidant properties. 16S rDNA sequencing of feces from all groups of mice was performed to clarify the changes in the intestinal microbiota of mice before and after treatment with naringin, and the mechanism of naringin in treating IBD was analyzed by untargeted metabolomics.

Results

After naringin treatment, mice with IBD showed recovery of weight loss, decreased DAI, increased colon length and weight, decreased histopathological scores, down-regulation of cytokines, and decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity (IDDF2024-ABS-0317 Figure 1. Effect of naringin in the treatment of IBD), 16S rDNA sequencing showed reversals of both diversity and composition of the intestinal flora, with an increase in the abundance of the phylum Firmicutes and Bacteroidetes, which was close to that of the control, as well as a significant increase in the abundance of Lactobacillus and Bifidobacterium, and metabolomics analysis showed that the pathways associated with naringenin treatment could be the biosynthesis of bile acids and butyrate, and the metabolism of tryptophan (IDDF2024-ABS-03171 Figure 2. 6S rDNA and untargeted metabolomics analysis results).

Conclusions

By modulating the composition and metabolism of the intestinal microbiota, oral administration of naringin in appropriate doses effectively attenuated IBD and improved the colonic mucosal barrier function in mice. Naringin may treat IBD by affecting the biosynthesis of bile acids and butyrate, and the metabolism of tryptophan.