@article {Jin777, author = {Un-Ho Jin and Syng-Ook Lee and Gautham Sridharan and Kyongbum Lee and Laurie A. Davidson and Arul Jayaraman and Robert S. Chapkin and Robert Alaniz and Stephen Safe}, title = {Microbiome-Derived Tryptophan Metabolites and Their Aryl Hydrocarbon Receptor-Dependent Agonist and Antagonist Activities}, volume = {85}, number = {5}, pages = {777--788}, year = {2014}, doi = {10.1124/mol.113.091165}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The tryptophan metabolites indole, indole-3-acetate, and tryptamine were identified in mouse cecal extracts and fecal pellets by mass spectrometry. The aryl hydrocarbon receptor (AHR) agonist and antagonist activities of these microbiota-derived compounds were investigated in CaCo-2 intestinal cells as a model for understanding their interactions with colonic tissue, which is highly aryl hydrocarbon (Ah){\textendash}responsive. Activation of Ah-responsive genes demonstrated that tryptamine and indole 3-acetate were AHR agonists, whereas indole was an AHR antagonist that inhibited TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin){\textendash}induced CYP1A1 expression. In contrast, the tryptophan metabolites exhibited minimal anti-inflammatory activities, whereas TCDD decreased phorbol ester-induced CXCR4 [chemokine (C-X-C motif) receptor 4] gene expression, and this response was AHR dependent. These results demonstrate that the tryptophan metabolites indole, tryptamine, and indole-3-acetate modulate AHR-mediated responses in CaCo-2 cells, and concentrations of indole that exhibit AHR antagonist activity (100{\textendash}250 μM) are detected in the intestinal microbiome.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/85/5/777}, eprint = {https://molpharm.aspetjournals.org/content/85/5/777.full.pdf}, journal = {Molecular Pharmacology} }