Ulcerative colitis (UC) is an
inflammatory bowel disease (IBD) that causes long-term
inflammation and
ulcers in the colon and rectum. Approximately 3 million adults were diagnosed with IBD in the US in 2015, and its incidence rate is estimated to increase by 4-6 times in 2030. Industrial
pollutants are largely responsible for this significant increase in UC cases. Several epidemiological and animal studies have demonstrated the correlation between
pollutants and
gastrointestinal diseases, but detailed molecular mechanisms responsible for adverse effects of
environmental pollutants on UC are still unknown. In the present study, we used a
dextran sulfate sodium (DSS)-induced
colitis mouse model, comparative metabolomics analysis, and systematic bioinformatics analysis to delineate the synergistic adverse effects of
bisphenol A (BPA) and its substitute
fluorene-9-bisphenol (BHPF) on UC. Subsequently, a significant alteration in gut metabolites was observed by the BPA and BHPF treatments. Furthermore, the bioinformatics analysis indicated deregulation of
sugar and
fatty acid metabolisms in the DSS-induced
colitis model by the BPA and BHPF treatments, respectively. Additionally, both the treatments induced an inflammatory response in the model. Particularly, some DSS-deregulated metabolites, which play important roles in gut
inflammation, were synergistically induced or reduced by the BPA and BHPF treatments. To the best knowledge of the authors, the synergistic adverse effects of the BPA and BHPF treatments on UC were demonstrated for the first time through gut metabolism alterations. Therefore, the present study provides novel insights in the role of
environmental pollutants, such as BPA and BHPF, in UC development.