AbstractBackgroundAlthough diabetes mellitus (DM) is regarded as a risk factor of colorectal cancer (CRC), the impacts of pre‐existing DM on CRC without drug intervention remain unknown. The purpose of this study was to investigate and analyze the effects of diabetes mellitus (DM) on colorectal cancer (CRC). And, to further explore the influencing factors and the mechanisms of DM affects CRC progression.MethodsIn this study, we investigated the effects of DM on CRC progression in a streptozotocin‐induced DM mice model. Furthermore, we evaluated the change of T cells levels using flow cytometry and indirect immunofluorescence. We assessed the alternation of gut microbiome and the transcriptional response using 16s rRNA sequencing and RNA‐seq.ResultsResults showed that the mice survival time was significantly decreased in CRC complicated with DM group (DM‐CRC), compared with only tumor bearing mice (CRC group). Furthermore, we found that DM could affect the immune response by changing the infiltration of CD4+T cells, CD8+T cells and mucosal‐associated invariant T cell (MAIT) in the CRC progression. In addition, DM could induce gut microbiome dysbiosis and change the transcriptional response in CRC complicated with DM.ConclusionFor the first time, the effects of DM on CRC were systematically characterized in a mice model. Our findings highlight the effects of pre‐existing DM on CRC, and these findings should facilitate further studies in exploring and developing potentially targeted therapy for CRC in diabetic patients. Our results suggest that the effects induced by DM should be considered in the treatment for CRC complicated with DM patients.