DHA Exacerbates Experimentally Induced Colitis in SMAD3−/− Mice

Abstract

Inflammatory bowel disease (IBD) increases the risk of developing colorectal cancer. It is hypothesized that dietary interventions can reduce inflammation and associated cancer risk. The long chain omega‐3 fatty acid, docosahexaenoic acid (DHA) has potent anti‐inflammatory properties. The objective of this study was to determine whether dietary DHA could reduce experimentally induced colitis and subsequent colon cancer risk. We utilized a mouse model of colitis and colon adenocarcinoma formation (SMAD3−/−). When SMAD3−/− mice are exposed to H. hepaticus, colitis is observed 4 wks post infection. Mice (10 per group) were fed AIN‐93G powdered diets supplemented with corn oil, safflower oil, or DHA‐rich fish oil (doses ranging from 0.75–6%) for 8 wks. Mice were then gavaged with H. hepaticus, continued on their diets and sacrificed 4 weeks post‐infection. Colon and cecal tissue were collected for histopathology and scored for inflammation and dysplasia. Spleen, peyers patch and mesenteric lymph nodes were collected for CD3+ cell populations. Contrary to expectations, DHA (2.25–6%) induced severe colitis and adenocarcinoma formation. Increased severity of colitis in DHA fed mice was associated with a CD8+ driven response to bacterial infection. These results suggest that DHA supplementation in immune‐associated diseases like IBD should be approached with caution.