FICZ activating AHR protects against intestinal injury in mice with DSS-induced colitis by regulating intestinal flora and metabolism

Abstract

Abstract Background: Aromatic hydrocarbon receptors (AHR) are widely expressed in the intestinal barrier and play a regulatory role in intestinal inflammation and immunity. Objectives: In this study, a dextran sulfate (DSS)-induced colitis mouse model was established to detect the effects of AHR activation on the intestinal barrier, flora, and metabolites. Design: The mice were randomly divided into three groups: Control group, DSS group, and DSS- formylindole (3,2-b) carbazole (FICZ) group. The Control group accepted sterile distilled water, the DSS group received 3%DSS, and the DSS-FICZ group were provided 3% of DSS and intraperitoneal injection of FICZ (1ug / mouse / day). Methods: The mental state and the fecal traits were observed, the basic living characteristic occult blood and inflammatory cytokine levels in the serum were detected. Fecal samples were collected for gut microbiota and metabolite analysis by 16S rRNA gene sequencing and LC–MS metabolomics. Results: AHR activation significantly improved the degree of colon shortening in DSS-induced colitis mice, reduced the degree of intestinal mucosal barrier damage, the production of inflammatory factors, and the intestinal epithelial permeability, and increased the tight junction protein expression. The results of 16S rRNA gene sequencing found that, compared with the DSS group, the abundance of Desulfobacterota was up-regulated in the DSS-FICZ group, and the abundance of Proteobacteria was down-regulated at the phylum level. At the genus level, Escherichia-Shigella was down-regulated, Clostridia _ UCG-014, Alistipes, andParabacteroides were up-regulated. At the species level, Escherichia _ coli _ g _ Escherichia-Shigella，Bacteroides _ sartorii _ g _ Bacteroides，Paeniclostridium _ sordellii _ g _ Paeniclostridium and Clostridium _ perfringens _ g _ Clostridium _ sensu _ stricto _ 1 were down-regulated; Bacteroides _ dorei _ g _ Bacteroides was up-regulated, Helicobacter _ hepaticus _ g _ Helicobacter, and Bacteroides _ caecimuris _ g _ Bacteroides was up-regulated, Parabacteroides _ distasonis _ g _ Parabacteroides were down-regulated. LC-MS metabolomics detection revealed that there were differences in a variety of intestinal contents between DSS group and DSS-FICZ group, which was mainly related to histidine metabolism, arginine biosynthesis, lysine degradation, and steroid biosynthesis. Conclusion: The activation of AHR can protect against intestinal injury in mice with DSS-induced colitis by regulating intestinal flora and metabolism.