Dietary acrylamide exposure increases susceptibility to ulcerative colitis: A comprehensive analysis from network toxicology to in vivo experimental validation.

Acrylamide (AA) is a contaminant present in foods cooked at high temperatures, and its formation is associated with the Maillard reaction. Ulcerative colitis (UC) is a chronic inflammatory disease of the colon mucosa with a complex pathogenesis. This study investigated the effects of AA exposure on UC and its potential mechanisms. First, network toxicology was employed to identify genes that are targets associated with both the toxicity of AA and the pathogenesis of UC, which are enriched in pathways associated with inflammatory cascades and immune cell recruitment. Then, Mendelian randomization was employed to identify two risk proteins (CCL5 and CXCL10) associated with AA and UC. Molecular docking and molecular dynamics simulations revealed that CXCL10 exhibits the strongest binding affinity with AA, and the complex is stable. Furthermore, animal studies have found that AA exposure alone does not induce typical colitis manifestations in mice. However, AA exposure exacerbated the colitis phenotype in the DSS-induced model. CXCL10 has been identified as a potential key target in the process by which AA increases susceptibility to UC. These findings provide scientific grounds for reassessing the safety of AA and offer new insights into understanding the environmental risks of UC and potential intervention targets.