Long-term hexavalent chromium exposure facilitates colorectal cancer in mice associated with changes in gut microbiota composition

Abstract

Colorectal cancer (CRC) is among the leading causes of cancer-related mortality worldwide. Hexavalent chromium [Cr(VI)] is often present in groundwater. Chronic Cr(VI) exposure is suggested to be one of the main factors inducing cancer. However, the correlation between Cr(VI) and CRC remains unclear. In this study, we investigated the role of Cr(VI) in CRC by establishing a mouse CRC model induced by 1, 2-dimethylhydrazine (DMH). The results showed that Cr(VI) increased weight loss in DMH-induced mice and promoted the formation of tumors. Cr(VI) also increased DMH-induced proliferating cell nuclear antigen (PCNA) levels. Investigation of the underlying mechanisms found that Cr(VI) significantly decreased DMH-induced SOD, GSH and CAT levels, while, the MDA level increased. Metagenomic analyses found that the abundance of Firmicutes and Bacteroidetes in the DMH + Cr group was down-regulated. Interestingly, the combination of Cr(VI) and DMH significantly increased the abundance of Verrucomicrobia. At the family and genus levels, families Akkermansiaceae and Saccharimonadaceae and genus Akkermansia were more abundant in the DMH + Cr group, whereas the abundance of short-chain fatty acid (SCFA)-producing bacteria (family Muribaculaceae, family Lachnosipiraceae, genus Lachnospiraceae_NK4A136_group, and genus Roseburia) decreased. These results indicate that Cr(VI) might aggravate CRC by altering the composition of the gut microflora.