M1002 protect mice from DSS-induced colitis through regulation of HIF-1 signaling and the Gut Microbiota in DSS-Induced Colitis in Mice

Abstract. Ulcerative colitis (UC) is an intestinal disease characterized by chronic recurrent inflammation, but the underlying mechanism remains undefined and requires in-depth exploration. The aim of the present study was to investigate the biological effects of a small molecular compound M1002 of oxygen-sensing signaling pathway on dextran sulfate sodium (DSS)-induced intestinal inflammation colitis mouse models. It was found that the protective effects of M1002 on DSS-induced colitis. To determine how M1002 exerted its protective effect in DSS-induced colitis, we compared the global gene expression profiles in the gut between DSS control and M1002 treatment colitis mouse groups by RNA-Seq. The results demonstrated that HIF-1 signaling pathway-related genes were significantly upregulated in the gut of M1002 treatment colitis mice, whereas the Inflammatory bowel disease signaling pathway, the TNF signaling pathway, and Cytokines and inflammatory response signaling pathway related genes were significantly downregulated in the M1002 treatment group. 16S rRNA gene sequencing demonstrated remarkable variations in the composition of gut microbiota between DSS control and M1002 treatment colitis mice. Compared with DSS control colitis mice, the relative abundance of Eubacterium_nodatum and Halomonas in the gut microbiota was significantly increased at genus level in the gut of M1002 treatment colitis mice. Based on these findings, we tend to conclude that M1002 might alleviate DSS-induced gut injury in mice by regulation of HIF-1 signaling and up-regulating Eubacterium_nodatum and Halomonas. The findings of the present study provide deep insights into the molecular mechanisms of protective effects of a small molecular compound of oxygen-sensing signaling pathway M1002 for DSS-induced colitis. On this basis, this research depicted remarkable variations in the number of gut microbiota between the DSS control and M1002 treatment mouse groups via 16S rRNA gene sequencing. There were abundant Eubacterium_nodatum and Halomonas in the gut microbiota of M1002 treatment colitis mouse groups. Collectively, we hypothesize that M1002 might alleviate DSS-induced gut injury in mice by regulation of HIF-1 signaling and up-regulating Eubacterium_nodatum and Halomonas.