Cadmium exposure elevates gut microbial oleic acid and promoted colitis potentially via FFAR4: A network toxicology...

Cadmium (Cd) could cause damage on colon promoting inflammatory bowel disease (IBD) through drinking and dietary intake. Cadmium has been proved disturbed the composition and diversity of gut microbiota in mice and enhance the production of bacterial metabolite, oleic acid. However, the modification of oleic acid content in the gut bacterial metabolites when exposed to cadmium needs to be verified, as well as the mechanism of cadmium toxicity on colitis. Thus, we determined the content of oleic acid in gut bacterial metabolites of mice exposed to cadmium and analyzed the core target of Cadmium, oleic acid and IBD to find the mechanism of cadmium toxic effect on promoting DSS-induced intestinal inflammation. In mice exposed to cadmium, oleic acid content in gut microbiota metabolites was significantly increased. Network toxicology analysis found 74 common genes between cadmium and oleic acid, and further identified the core targets of these 74 genes and IBD targets, counting for 53 genes. According to these data, we identified the major genes, including IL1B, BCL2, TNF, IL6 and TP53, and pathways, such as regulation of apoptotic signaling pathway, lipid and atheroscleorsis, involved in cadmium promoted colitis, and the vital receptor, FFAR4, of oleic acid receptor. The blockage of FFAR4 by AH7614 obviously inhibited the DSS-induced colitis exacerbated by cadmium. In conclusion, this study demonstrates cadmium elevates the content of oleic acid in gut microbiota and the mechanism underlying cadmium-aggravated colitis potentially by FFAR4.