Fish Oil Alters T Lymphocyte Cell Populations and cerbates Disease in a Mouse Model of R mmatory Colitis

Downlo mmatory bowel diseases (IBD) increase the risk of developing colorectal cancer. Dietary components duce inflammation are associated with lower cancer risk. The long-chain omega-3 fatty acid docosaoic acid (DHA) is present in fish oil and has potent anti-inflammatory properties. The objective of this is to determine whether dietary fish oil enriched with DHA (DFO) could reduce experimentally induced and colon cancer risk in a mouse model. When SMAD3−/− mice are exposed to Helicobacter hepaticus, olitis is observed 4 weeks postinfection. Mice were fed isocaloric diets modified to include corn oil, er oil, or DFO (doses ranging from 0.75% to 6.00%) as the fatty acid source for 8 weeks. Mice were d with H. hepaticus; DFO feeding was continued; and mice were sacrificed 4 weeks after infection. lon and cecum were collected for histopathology. Spleens and mesenteric lymph nodes were collected alyzed for T-cell populations using flow cytometry. Contrary to expectations, DFO induced severe colitis enocarcinoma formation. DFO consumption was associated with decreased CD8 cell frequency and ished CD69 expression on CD4 and CD8 T-cell populations. Mice consuming DFO also exhibited higher + CD25 CD4 T regulatory cell frequency, FoxP3 expression, and altered L-selectin expression during ion. We concluded that DFO-fed mice may be less equipped to mount a successful response to aticus infection, increasing colon cancer risk. These results support the need to establish a tolerable H. hep upper limit for DHA intake particularly in the context of chronic inflammatory conditions such as IBD. Cancer Res; 70(20); 7960–9. ©2010 AACR.