091 | Increased vulnerability to experimental colitis following chronic low-dose exposure to Sicilian environmental contaminants

Noemi Aloi^1|2, Paolo Colombo², Valeria Longo², Rosa Serio¹, Maria Grazia Zizzo¹ | ¹Department of Biological, Chemical and Pharmaceutical Sciences and Technologies STEBICEF, Università di Palermo, Italy; ²Institute for Biomedical Research and Innovation, National Research Council of Italy IRIB-CNR, Palermo, Italy.

Industrial expansion and economic growth have markedly intensified the release of chemical contaminants into the environment, raising increasing concern about their contribution to immune dysregulation and the development of non-communicable diseases (NCDs), including inflammatory bowel diseases (IBDs).^1,2 Among these contaminants present in the anthropogenic area of Sicily, brominated flame retardants and steroidal estrogens are of relevance due to their endocrine- and immune-disrupting properties. The gastrointestinal tract represents a highly vulnerable target for chronic environmental stressors, and long-term exposure to low levels of pollutants may predispose individuals to intestinal inflammatory disorders. In this study, we evaluated the impact of prolonged, low-dose oral exposure to a mixture of two widespread environmental contaminants in Sicily—2,2’,4,4’-tetrabromodiphenyl ether (BDE-47³) and estrone (E1⁴)—on intestinal susceptibility to inflammation as observed in the regulation of macrophage immune response.⁵  Wistar rats were administered the pollutant mixture (MIX1: BDE-47 0.01 mg/kg and E1 1 ng/kg; MIX2: BDE-47 0.1 mg/kg and E1 10 ng/kg) for 30 or 60 days prior to the induction of experimental colitis by intrarectal DNBS. Intestinal tissues were subsequently examined to assess macroscopic damage, inflammatory activity, and epithelial barrier integrity. While chronic exposure to the pollutant mixture alone did not cause evident intestinal alterations, it significantly worsened the severity of colitis induced by DNBS. After 30 days of exposure, rats exhibited greater body weight loss, reduced food intake, and increased myeloperoxidase (MPO) activity compared to DNBS-treated controls, indicating enhanced neutrophil infiltration. These adverse effects were further intensified after 60 days of exposure, leading to more pronounced macroscopic signs of intestinal injury. Molecular analyses are ongoing to identify signaling pathway and molecular component involved. Overall, our findings demonstrate that sustained exposure to environmentally relevant doses of chemical contaminants can sensitize the gut to inflammatory insults, thereby aggravating disease outcomes. These data underscore the critical need to incorporate chronic, low-dose exposure scenarios into environmental risk assessments for complex, multifactorial diseases such as IBD.