Mycotoxins are fungal secondary metabolites that contaminate a wide spectrum of foods worldwide. Mycotoxins exert a diversity of human health threats, including carcinogenesis with the most common & pathologically-significant mycotoxins being aflatoxins, fumonisins, trichothecenes (e.g. deoxynivalenol (DON)) & patulin (PAT). MYCOLON is based on preliminary data identifying DON & PAT as mycotoxins with the highest potential to affect the gut epithelial barrier, interact with human colon carcinoma cells and induce systemic & local gut inflammation, suggesting their involvement in colorectal & colitis-associated cancer (CRC/CAC). In addition, the investigation of a European cohort (n=476,160) demonstrated a significantly increased CRC risk with DON & PAT. Studies investigating causal relationships between mycotoxin exposure & CRC are limited to in vitro studies, while in vivo studies are non-existent. Therefore, MYCOLON aims to mechanistically investigate the tumor-promoting effects of (multiple) mycotoxin exposures (DON & PAT) on intestinal epithelial cells using in vivo mouse models of CRC/CAC and murine, as well as human, intestinal organoids from colonic adenocarcinomas. Resulting causal relationships will form a basis for future strategies for early detection of human carcinogenesis, and prevention by identification of specific risks related to multiple mycotoxin exposure.