P1335 Dietary Carnosic Acid Eases Colitis by Activating NRF2 Signal via Regulating Gut Microbiota and Metabolites
Authors: Xiaohan W , feng T 
Published: January 2025

Background

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease, which is closely related to the imbalance of intestinal microbiota and metabolic alterations. We have studied the role of dietary carnosic acid (CA) in alleviating intestinal inflammation through regulating the intestinal microbiota and its metabolites.

Methods

Mice were fed with a diet supplemented with CA or a normal diet, and the enteritis model was established using dextran sulfate sodium (DSS). The feces of mice fed with different diets were transplanted into germ-free mice to determine the direct role of the CA-regulated microbiota in alleviating colitis. The intestinal microbiota was analyzed by 16S rRNA sequencing, serum metabolites were analyzed by liquid chromatography-mass spectrometry (LC-MS) metabolomics, and downstream targets were analyzed by RNA sequencing.

Results

Through the analysis of the microbiota based on the 16S rRNA gene, we found for the first time that the addition of CA to the diet improved the imbalance of the intestinal microbiota induced by DSS. The protective mechanism of CA against DSS-induced colitis is to improve the function of the intestinal mucosal barrier by activating the Nrf2 signaling pathway. It is worth noting that the addition of CA to the diet can enrich the microbe-derived 3-indolepropionic acid, thereby activating the Nrf2 signaling in human colonic epithelial cells. In addition, exogenous 3-indolepropionic acid treatment has a similar protective effect on DSS-induced colitis by improving the Nrf2 signaling-dependent mucosal barrier function.

Conclusion

In conclusion, our research results indicate that the intestinal microbiota - 3-indolepropionic acid - Nrf2 axis plays an important role in maintaining intestinal homeostasis, which may represent a new method for preventing colitis by manipulating the metabolites of the intestinal microbiota.

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