Loss of n‐6 fatty acid induced pediatric obesity protects against acute murine colitis

Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases (IBDs): Crohn disease (CD) and ulcerative colitis (UC). Dietary n‐6 fatty acids have been associated with UC in prospective studies. However, the critical...

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Published in:The FASEB journal 2015-08, Vol.29 (8), p.3151-3159
Main Authors: Nagy‐Szakal, Dorottya, Mir, Sabina A. V., Harris, R. Alan, Dowd, Scot E., Yamada, Takeshi, Lacorazza, H. Daniel, Tatevian, Nina, Smith, C. Wayne, Zoeten, Edwin F., Klein, John, Kellermayer, Richard
Format: Article
Language:English
Subjects:
Animals
Colitis - metabolism
Colon - metabolism
CXCL13
Diet
Fatty Acids, Omega-6 - metabolism
inflammatory bowel disease
Intestinal Mucosa - metabolism
Male
Mice
Mice, Inbred C57BL
microbiome
Pediatric Obesity - metabolism
Prospective Studies
Research Communication
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Summary:Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases (IBDs): Crohn disease (CD) and ulcerative colitis (UC). Dietary n‐6 fatty acids have been associated with UC in prospective studies. However, the critical developmental period when (n‐6) consumption may induce UC is not known. We examined the effects of transiently increased n‐6 consumption during pediatric development on subsequent dextran‐sulfate‐sodium (DSS)‐induced acute murine colitis. The animals transiently became obese then rapidly lost this phenotype. Interestingly, mice were protected against DSS 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 (Cxc1)13 (the ligand of Cxcr5) antibody treatment decreased DSS 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 IBD patients. The human serologic observations supported the translational relevance of our findings.—Nagy‐Szakal, D., Mir, S. A. V., Harris, R. A., Dowd, S. E., Yamada, T., Lacorazza, H. D., Tatevian, N., Smith, C. W., de Zoeten, E. F., Klein, J., Kellermayer, R. Loss of n‐6 fatty acid induced pediatric obesity protects against acute murine colitis. FASEB J. 29, 3151‐3159 (2015). www.fasebj.org
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.14-267690