title: Caspase recruitment domain 9, microbiota, and tryptophan metabolism: dangerous liaisons in inflammatory bowel diseases.
abstract: OBJECTIVE
  Inflammatory bowel diseases (IBDs) develop as a result of a combination of genetic predisposition, dysbiosis of the gut microbiota, and environmental influences. Here, we describe an example of how caspase recruitment domain 9 (CARD9), one of the numerous IBD susceptibility genes, participate to colitis susceptibility by shaping gut microbiota to produce tryptophan metabolites.
  
  
  RESULTS
  Recent study showed that CARD9 mice are more susceptible to colitis as a result of impaired interleukin 22 signaling pathway. Furthermore, aryl hydrocarbon receptor (AhR) ligands from tryptophan metabolism by the gut microbiota participate to intestinal homeostasis by inducing production of interleukin 22 by intestinal immune cells. These data suggest an interaction between CARD9 and the ability of gut microbiota to produce AhR ligands.
  
  
  CONCLUSIONS
  The microbiota from CARD9 mice fails to metabolize tryptophan leading to defective AhR activation which contributes to the susceptibility of mice to colitis by decreased interleukin 22 production. These effects were abrogated in the presence of AhR agonist. Reduced production of AhR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. Correcting impaired microbiota functions, such as ability to produce AhR ligands, is an attractive strategy in IBD.
authors.affiliation: aSorbonne University-Pierre and Marie Curie University bINSERM ERL 1157, Avenir Team Gut Microbiota and Immunity cCNRS UMR 7203 dLaboratoire de BioMolécules (LBM), CHU Saint-Antoine eMicalis Institute, INRA, Agro Paris Tech, Université Paris-Saclay, Jouy-en-Josas fInflammation-Immunopathology-Biotherapy Department (DHU i2B) gDepartment of Gastroenterology, Saint Antoine Hospital, Assistance Publique-Hopitaux de Paris, Pierre and Marie Curie University, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lamas
authors.forename: Mathias L
authors.initials: ML
authors.lastname: Richard
authors.forename: Harry
authors.initials: H
authors.lastname: Sokol
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics* / Q000502:physiology; D003092:Colitis / Q000235:genetics / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000382:microbiology; D007378:Interleukins / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D053468:CARD Signaling Adaptor Proteins; D007378:Interleukins; D018336:Receptors, Aryl Hydrocarbon; D014364:Tryptophan; D000097043:Interleukin-22; C505855:CARD9 protein, human