Location: Children's Nutrition Research CenterTitle: Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis
|NAGY-SZAKAL, D - Children'S Nutrition Research Center (CNRC)|
|MIR, SA - Baylor College Of Medicine|
|HARRIS, RA - Baylor College Of Medicine|
|DOWD, SE - Molecular Research Lp (MR DNA)|
|YAMADA, T - Baylor College Of Medicine|
|LACORAZZA, HD - Baylor College Of Medicine|
|TATEVIAN, N - Baylor College Of Medicine|
|SMITH, CW - Children'S Nutrition Research Center (CNRC)|
|DE ZOETEN, EF - Baylor College Of Medicine|
|KLEIN, J - University Of Texas Health Science Center|
|KELLERMAYER, R - Children'S Nutrition Research Center (CNRC)|
Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/22/2015
Publication Date: 8/20/2015
Citation: Nagy-Szakal, D., Mir, S., Harris, R., Dowd, S., Yamada, T., Lacorazza, H., Tatevian, N., Smith, C., De Zoeten, E., Klein, J., Kellermayer, R. 2015. Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis. Journal of Federation of American Societies for Experimental Biology. 29:3151-3159.
Interpretive Summary: Mice were used to study the influence of the gut microbiome (the mix of bacteria in the intestines) on inflammation of the large intestines (the colon). Feeding young mice a diet rich in a type of fat called n-6 fatty acids for 50 days followed by a normal diet for 40 days resulted in a persistent change in the gut microbiome and an increased resistance to development of an experimental type of inflammation of the colon. This study indicates that transient dietary changes during early periods of development can lead to prolonged changes in the gut microbiome and in resistance to intestinal inflammation.
Technical Abstract: Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases: Crohn disease and ulcerative colitis. Dietary n-6 fatty acids have been associated with ulcetative colitis in prospective studies. However, the critical developmental period when (n-6) consumption may induce ulcerative colitis is not known. We examined the effects of transiently increased n-6 consumption during pediatric development on subsequent dextran-sulfate-sodium induced acute murine colitis. The animals transiently became obese then rapidly lost this phenotype. Interestingly, mice were protected against dextran-sulfate-sodium colitis 40 days after n-6 consumption. The transient high n-6-induced protection against colitis was fat type- and dietary reversal-dependent and could be transferred to germ-free mice by fecal microbiota transplantation. We also detected decreased numbers of chemokine receptor (Cxcr)5(+) CD4(+) T cells in the mesenteric lymph nodes (MLNs) of transiently n-6-fed mice. Further experiments revealed that anti-chemokine ligand (Cxcl)13 (the ligand of Cxcr5) antibody treatment decreased dextran-sulfate-sodium colitis severity, implicating the importance of the Cxcr5-Cxcl13 pathway in mammalian colitis. Consecutively, we found elevated CXCL13 concentrations (CD: 1.8-fold, P = 0.0077; UC: 1.9-fold, P = 0.056) in the serum of untreated pediatric inflammatory bowel diseases patients. The human serologic observations supported the translational relevance of our findings.