Abstract

The increasing environmental concentration of the organophosphate ester 2-ethylhexyl diphenyl phosphate (EHDPHP) poses a threat to global health, particularly for individuals with preexisting conditions such as inflammatory bowel disease (IBD). This study investigated the impact of EHDPHP on a dextran sulfate sodium (DSS)-induced colitis mouse model. We found that EHDPHP exposure significantly aggravated disease severity and was associated with a marked upregulation of microRNA-155 (miR-155) in the colon. To elucidate the role of miR-155 in this process, we utilized miR-155 gene knockout (miR-155 -/- ) mice. Our results demonstrate that miR-155 knockout protected against EHDPHP-exacerbated colitis by inhibiting apoptosis and suppressing the proinflammatory JAK-STAT-p53 signaling axis, and this process is closely linked to shifts in gut microbiota abundance. Conversely, miR-155 overexpression reverses these protective effects. These findings establish miR-155 as a critical mediator in the aggravation of colitis by environmental pollutants and suggest that targeting miR-155 may represent a potential therapeutic target for pollutant-aggravated inflammatory bowel disease.