Institute of Biosciences and Technology, Texas A&M Health Sciences Center, Houston, Texas (U.-H.J., S.-O.L., S.S.); Department of Microbial and Molecular Pathogenesis, Texas A&M University Health Sciences Center (A.J., R.A.), Department of Veterinary Physiology and Pharmacology (S.S.), Department of Chemical Engineering (A.J.), and Department of Nutrition and Food Science (L.A.D., R.S.C.), Texas A&M University, College Station, Texas; Department of Food Science and Technology, Keimyung University, Daegu, Republic of Korea (S.-O.L.); and Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts (G.S., K.L.).
Mol Pharmacol. 2014 May;85(5):777-88. doi: 10.1124/mol.113.091165. Epub 2014 Feb 21.
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)-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)-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 (100-250 μM) are detected in the intestinal microbiome.
色氨酸代谢物吲哚、吲哚-3-乙酸和色胺通过质谱在小鼠盲肠提取物和粪便颗粒中被鉴定出来。这些微生物衍生化合物的芳基烃受体 (AHR) 激动剂和拮抗剂活性在 CaCo-2 肠细胞中进行了研究，作为理解它们与高度芳基烃 (Ah) 反应性的结肠组织相互作用的模型。Ah 反应性基因的激活表明色胺和吲哚 3-乙酸是 AHR 激动剂，而吲哚是抑制 TCDD（2,3,7,8-四氯二苯并-p-二恶英）诱导的 CYP1A1 表达的 AHR 拮抗剂。相比之下，色氨酸代谢物表现出最小的抗炎活性，而 TCDD 降低了佛波酯诱导的 CXCR4 [趋化因子 (C-X-C 基序) 受体 4] 基因表达，并且这种反应是 AHR 依赖性的。这些结果表明，色氨酸代谢物吲哚、色胺和吲哚-3-乙酸调节 CaCo-2 细胞中的 AHR 介导的反应，并且在肠道微生物组中检测到具有 AHR 拮抗剂活性的吲哚浓度（100-250 μM）。
