Cadmium accelerates bacterial oleic acid production to promote fat accumulation in Caenorhabditis elegans

Environmental cadmium, with a high dietary intake and long biological half-life, is a severe health risk by harming physiological function directly or through gut microbiota. However, the toxicity mechanisms of environmental cadmium on microbes and host systems remain unclear. Herein, we established three C. elegans and E. coli cultivated systems to investigate the vital role of microorganisms in cadmium-induced lipid toxicity and depict the interaction between environmental cadmium, bacteria, and the host. We found that only nematodes in the system with live bacteria, rather than UV-killed bacteria or no bacteria, could be induced to fat accumulation by cadmium exposure, suggesting that bacteria mediated the effect of environmental cadmium on body fat. Cadmium caused perturbation of metabolite in bacteria, most notably oleic acid, elevated the synthesis genes expression, and enhanced the bacterial oleic acid production, which further promoted the expression of lipid metabolism-related genes and fat deposition in C. elegans regardless of the cultivated system. Finally, we showed the potential protective effect of Vitamin D3 which prevented cadmium- or oleic acid-induced fat storage significantly. In conclusion, this study illustrates the mechanism underlying cadmium-induced lipid accumulation in body through bacterial metabolites and reveals the interplay between environmental cadmium, microorganisms, and the host.