Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
Sorbonne Universités, UPMC Univ Paris 06, IFD, 4 place Jussieu, 75252, Paris, cedex 05, France.
Sci Rep. 2019 Jan 24;9(1):643. doi: 10.1038/s41598-018-37019-2.
The ligand activated transcription factor, aryl hydrocarbon receptor (AhR) emerged as a critical regulator of immune and metabolic processes in the gastrointestinal tract. In the gut, a main source of AhR ligands derives from commensal bacteria. However, many of the reported microbiota-derived ligands have been restricted to indolyl metabolites. Here, by screening commensal bacteria supernatants on an AhR reporter system expressed in human intestinal epithelial cell line (IEC), we found that the short chain fatty acid (SCFA) butyrate induced AhR activity and the transcription of AhR-dependent genes in IECs. We showed that AhR ligand antagonists reduced the effects of butyrate on IEC suggesting that butyrate could act as a ligand of AhR, which was supported by the nuclear translocation of AhR induced by butyrate and in silico structural modelling. In conclusion, our findings suggest that (i) butyrate activates AhR pathway and AhR-dependent genes in human intestinal epithelial cell-lines (ii) butyrate is a potential ligand for AhR which is an original mechanism of gene regulation by SCFA.
配体激活转录因子，芳香烃受体（AhR），作为胃肠道免疫和代谢过程的关键调节因子而出现。在肠道中，AhR 配体的一个主要来源来自共生细菌。然而，许多报道的微生物衍生配体已局限于吲哚代谢物。在这里，我们通过在人肠上皮细胞系（IEC）中表达的 AhR 报告系统筛选共生菌上清液，发现短链脂肪酸（SCFA）丁酸盐诱导 AhR 活性和 AhR 依赖性基因在 IEC 中的转录。我们表明，AhR 配体拮抗剂降低了丁酸盐对 IEC 的作用，这表明丁酸盐可以作为 AhR 的配体，这得到了丁酸盐诱导的 AhR 核易位和计算机结构建模的支持。总之，我们的研究结果表明：（i）丁酸盐激活人肠上皮细胞系中的 AhR 途径和 AhR 依赖性基因；（ii）丁酸盐是 AhR 的潜在配体，这是 SCFA 调节基因的原始机制。
