title: Dietary fish oil alters T lymphocyte cell populations and exacerbates disease in a mouse model of inflammatory colitis.
abstract: Inflammatory bowel diseases (IBD) increase the risk of developing colorectal cancer. Dietary components that reduce inflammation are associated with lower cancer risk. The long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is present in fish oil and has potent anti-inflammatory properties. The objective of this study is to determine whether dietary fish oil enriched with DHA (DFO) could reduce experimentally induced colitis and colon cancer risk in a mouse model. When SMAD3-/- mice are exposed to Helicobacter hepaticus, mild colitis is observed 4 weeks postinfection. Mice were fed isocaloric diets modified to include corn oil, safflower oil, or DFO (doses ranging from 0.75% to 6.00%) as the fatty acid source for 8 weeks. Mice were gavaged with H. hepaticus; DFO feeding was continued; and mice were sacrificed 4 weeks after infection. The colon and cecum were collected for histopathology. Spleens and mesenteric lymph nodes were collected and analyzed for T-cell populations using flow cytometry. Contrary to expectations, DFO induced severe colitis and adenocarcinoma formation. DFO consumption was associated with decreased CD8(+) cell frequency and diminished CD69 expression on CD4(+) and CD8(+) T-cell populations. Mice consuming DFO also exhibited higher FoxP3(+) CD25(+) CD4(+) T regulatory cell frequency, FoxP3 expression, and altered L-selectin expression during infection. We concluded that DFO-fed mice may be less equipped to mount a successful response to H. hepaticus infection, increasing colon cancer risk. These results support the need to establish a tolerable upper limit for DHA intake particularly in the context of chronic inflammatory conditions such as IBD.
authors.affiliation: Department of Food Science and Human Nutrition, Department of Pathobiology and Diagnostic Investigation, and College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Hillary L
authors.initials: HL
authors.lastname: Woodworth
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: McCaskey
authors.forename: David M
authors.initials: DM
authors.lastname: Duriancik
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Clinthorne
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Langohr
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Gardner
authors.forename: Jenifer I
authors.initials: JI
authors.lastname: Fenton
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000187:drug effects; D000945:Antigens, Differentiation, T-Lymphocyte / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D003106:Colon / Q000187:drug effects / Q000276:immunology; D003110:Colonic Neoplasms / Q000517:prevention & control; D003314:Corn Oil / Q000494:pharmacology; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology*; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D037181:Lectins, C-Type / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D012007:Rectum / Q000187:drug effects / Q000276:immunology; D051900:Smad3 Protein / Q000172:deficiency / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D003314:Corn Oil; D004042:Dietary Fats, Unsaturated; D004281:Docosahexaenoic Acids; D005395:Fish Oils; D037181:Lectins, C-Type; D051900:Smad3 Protein; D000099192:CD69 Antigens; C497791:Smad3 protein, mouse