title: Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22.
abstract: Endogenous tryptophan (Trp) metabolites have an important role in mammalian gut immune homeostasis, yet the potential contribution of Trp metabolites from resident microbiota has never been addressed experimentally. Here, we describe a metabolic pathway whereby Trp metabolites from the microbiota balance mucosal reactivity in mice. Switching from sugar to Trp as an energy source (e.g., under conditions of unrestricted Trp availability), highly adaptive lactobacilli are expanded and produce an aryl hydrocarbon receptor (AhR) ligand-indole-3-aldehyde-that contributes to AhR-dependent Il22 transcription. The resulting IL-22-dependent balanced mucosal response allows for survival of mixed microbial communities yet provides colonization resistance to the fungus Candida albicans and mucosal protection from inflammation. Thus, the microbiota-AhR axis might represent an important strategy pursued by coevolutive commensalism for fine tuning host mucosal reactivity contingent on Trp catabolism.
authors: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia 06132, Italy.
authors: Teresa
authors: T
authors: Zelante
authors: Rossana G
authors: RG
authors: Iannitti
authors: Cristina
authors: C
authors: Cunha
authors: Antonella
authors: A
authors: De Luca
authors: Gloria
authors: G
authors: Giovannini
authors: Giuseppe
authors: G
authors: Pieraccini
authors: Riccardo
authors: R
authors: Zecchi
authors: Carmen
authors: C
authors: D'Angelo
authors: Cristina
authors: C
authors: Massi-Benedetti
authors: Francesca
authors: F
authors: Fallarino
authors: Agostinho
authors: A
authors: Carvalho
authors: Paolo
authors: P
authors: Puccetti
authors: Luigina
authors: L
authors: Romani
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology; D004734:Energy Metabolism; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000172:deficiency / Q000235:genetics; D007211:Indoles / Q000378:metabolism; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics; D007378:Interleukins / Q000378:metabolism*; D052200:Limosilactobacillus reuteri / Q000254:growth & development / Q000276:immunology / Q000378:metabolism*; D054892:Metagenome; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D019936:Probiotics; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007211:Indoles; D020381:Interleukin-17; D007378:Interleukins; D053594:Myeloid Differentiation Factor 88; D018336:Receptors, Aryl Hydrocarbon; D051195:Toll-Like Receptor 2; D014364:Tryptophan; D000097043:Interleukin-22; C484722:Ahr protein, mouse; C583637:IDO1 protein, mouse; C098680:Il17a protein, mouse; C507780:Myd88 protein, mouse; C493486:Tlr2 protein, mouse; C012381:indole-3-carbaldehyde