title: Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis.
abstract: 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 (Cxcl)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.
authors.affiliation: *Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children Hospital, Houston, Texas, USA; U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA; Molecular Research LP, Shallowater, Texas, USA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas, USA; Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA; and **School of Dentistry, The University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Nagy-Szakal
authors.affiliation: *Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children Hospital, Houston, Texas, USA; U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA; Molecular Research LP, Shallowater, Texas, USA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas, USA; Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA; and **School of Dentistry, The University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Sabina A V
authors.initials: SA
authors.lastname: Mir
authors.affiliation: *Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children Hospital, Houston, Texas, USA; U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA; Molecular Research LP, Shallowater, Texas, USA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas, USA; Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA; and **School of Dentistry, The University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: R Alan
authors.initials: RA
authors.lastname: Harris
authors.affiliation: *Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children Hospital, Houston, Texas, USA; U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA; Molecular Research LP, Shallowater, Texas, USA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas, USA; Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA; and **School of Dentistry, The University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Scot E
authors.initials: SE
authors.lastname: Dowd
authors.affiliation: *Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children Hospital, Houston, Texas, USA; U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA; Molecular Research LP, Shallowater, Texas, USA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas, USA; Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA; and **School of Dentistry, The University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamada
authors.affiliation: *Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children Hospital, Houston, Texas, USA; U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA; Molecular Research LP, Shallowater, Texas, USA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas, USA; Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA; and **School of Dentistry, The University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: H Daniel
authors.initials: HD
authors.lastname: Lacorazza
authors.affiliation: *Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children Hospital, Houston, Texas, USA; U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA; Molecular Research LP, Shallowater, Texas, USA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas, USA; Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA; and **School of Dentistry, The University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Tatevian
authors.affiliation: *Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children Hospital, Houston, Texas, USA; U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA; Molecular Research LP, Shallowater, Texas, USA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas, USA; Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA; and **School of Dentistry, The University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: C Wayne
authors.initials: CW
authors.lastname: Smith
authors.affiliation: *Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children Hospital, Houston, Texas, USA; U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA; Molecular Research LP, Shallowater, Texas, USA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas, USA; Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA; and **School of Dentistry, The University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Edwin F
authors.initials: EF
authors.lastname: de Zoeten
authors.affiliation: *Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children Hospital, Houston, Texas, USA; U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA; Molecular Research LP, Shallowater, Texas, USA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas, USA; Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA; and **School of Dentistry, The University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: John
authors.initials: J
authors.lastname: Klein
authors.affiliation: *Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children Hospital, Houston, Texas, USA; U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA; Molecular Research LP, Shallowater, Texas, USA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA; Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, Texas, USA; Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA; and **School of Dentistry, The University of Texas Health Science Center, Houston, Texas, USA kellerma@bcm.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Kellermayer
mesh_terms: D000818:Animals; D003092:Colitis / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D004032:Diet; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D063766:Pediatric Obesity / Q000378:metabolism*; D011446:Prospective Studies
chemical_list: D043371:Fatty Acids, Omega-6
keywords: CXCL13; diet; inflammatory bowel disease; microbiome