title: Dietary tryptophan alleviates dextran sodium sulfate-induced colitis through aryl hydrocarbon receptor in mice.
abstract: Ulcerative colitis is the typical progression of chronic inflammatory bowel disease. Amino acids, particularly tryptophan, have been reported to exert a protective effect against colitis induced by dextran sodium sulfate (DSS), but the precise underlying mechanisms remain incompletely clarified. Tryptophan metabolites are recognized to function as endogenous ligands for aryl hydrocarbon receptor (Ahr), which is a critical regulator of inflammation and immunity. Thus, we conducted this study to investigate whether dietary tryptophan supplementation protects against DSS-induced colitis by acting through Ahr. Female wild-type (WT) and Ahr-deficient (knockout; KO) mice (10-12 weeks old) were divided into four groups and fed either a control or 0.5% tryptophan diet. The tryptophan diet ameliorated DSS-induced colitis symptoms and severity in WT mice but not in KO mice, and the diet reduced the mRNA expression of Il-6, Tnfα, Il-1β and the chemokines Ccl2, Cxcl1 and Cxcl2 in the WT groups. Furthermore, Il-22 and Stat3 mRNA expression in the colon was elevated in WT mice fed with the tryptophan diet, which mainly protected epithelial layer integrity, and Ahr also modulated immune homeostasis by regulating Foxp3 and Il-17 mRNA expression. These data suggest that tryptophan-containing diet might ameliorate DSS-induced acute colitis and regulate epithelial homeostasis through Ahr. Thus, tryptophan could serve as a promising preventive agent in the treatment of ulcerative colitis.
authors.affiliation: Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Jahidul
authors.initials: J
authors.lastname: Islam
authors.affiliation: Department of Biological Science and Technology, Tokyo University of Science, Tokyo, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Sato
authors.affiliation: Cellular Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; International Education and Research Center for Food Agricultural Immunology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Department of Food Science and Technology, Universitas Bakrie, Jakarta, Indonesia.
authors.lastname: Ardiansyah
authors.affiliation: Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hirahara
authors.affiliation: Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Aoyama
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
authors.affiliation: Cellular Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; International Education and Research Center for Food Agricultural Immunology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Aso
authors.affiliation: Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Komai
authors.affiliation: Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; International Education and Research Center for Food Agricultural Immunology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan. Electronic address: shirakah@m.tohoku.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shirakawa
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D019587:Dietary Supplements; D005260:Female; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014364:Tryptophan / Q000494:pharmacology*; D000097043:Interleukin-22
chemical_list: D018925:Chemokines; D016207:Cytokines; D016264:Dextran Sulfate; D007378:Interleukins; D009195:Peroxidase; D018336:Receptors, Aryl Hydrocarbon; D050796:STAT3 Transcription Factor; D014364:Tryptophan; D000097043:Interleukin-22; C494087:Stat3 protein, mouse
keywords: Aryl hydrocarbon receptor; Dextran sodium sulfate; Tryptamine; Tryptophan; Ulcerative colitis