Grant: Travel Awards - Institute Community Support

Background: Chronic inflammatory bowel disease (IBD) is a potential risk factor for prostate cancer, promoting systemic inflammation and microbial translocation. In IBD, dysbiosis promotes Enterobacteriaceae growth, including enteropathogenic E. coli (EPEC), which disrupts epithelial integrity and produces genotoxins like colibactin, causing DNA damage and oxidative stress. Suppressor of Cytokine Signaling 1 (SOCS1), a key inflammation regulator and tumor suppressor, is critical in these processes. SOCS1-deficient (Socs1fl/flPbCre) mice develop prostate hyperplasia and inflammation after puberty. This study investigates the impact of experimental colitis, dysbiosis, and systemic inflammation on their prostate glands. Methods: Colitis was induced in 8-12-week-old Socs1fl/flPbCre mice using dextran sulfate sodium (DSS). Prostate tissues were assessed via histology and immunohistochemistry for oxidative stress, DNA damage, and inflammation. Organoids from SOCS1-deficient and control mice were exposed to colibactin-producing EPEC and its mutant strain, with outcomes measured for oxidative stress, DNA damage, and inflammatory responses. Proteomic analysis of DSS-treated prostate organoids is ongoing. Results: DSS-treated Socs1fl/flPbCre mice exhibited typical colitis symptoms but displayed significant prostate gland pathology, including epithelial shedding, dysplasia, inflammation, hyperplasia, increased oxidative stress, and DNA damage. Organoids exposed to colibactin-producing EPEC showed higher DNA damage and oxidative stress compared to controls. Conclusions: DSS-induced colitis and microbial dysbiosis, particularly EPEC genotoxins, trigger pathological changes in SOCS1-deficient prostate epithelial cells, potentially leading to prostate cancer. This model provides a valuable tool to study the gut-prostate axis and evaluate interventions like probiotics and nutraceuticals.