Identification of the novel role of butyrate as AhR ligand in human intestinal epithelial cells
Identification of the novel role of butyrate as AhR ligand in human intestinal epithelial cells
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DOI：
10.1038/s41598-018-37019-2
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发表时间：
2019-01-24
影响因子：
4.6
通讯作者：
Lapaque, Nicolas
中科院分区：
文献类型：
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作者：
Marinelli, Ludovica;Martin-Gallausiaux, Camille;Lapaque, Nicolas
配体激活转录因子芳烃受体（AhR）作为胃肠道免疫和代谢过程的关键调节因子出现。在肠道中，AhR配体的主要来源是共生菌。然而，许多报道的微生物合成配体仅限于吲哚代谢物。本研究通过在人肠上皮细胞系（IEC）中表达的AhR报告系统上筛选共生菌上清液，发现短链脂肪酸（SCFA）丁酸盐可诱导IECs中AhR活性和AhR依赖基因的转录。我们发现AhR配体拮抗剂降低了丁酸盐对IEC的影响，这表明丁酸盐可以作为AhR的配体，这得到了丁酸盐诱导AhR核易位和硅结构模型的支持。综上所述，我们的研究结果表明：(1)丁酸盐激活人肠上皮细胞系中AhR通路和AhR依赖基因；(2)丁酸盐是AhR的潜在配体，是SCFA基因调控的一个原始机制。
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 microbiotaderived 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 AhRdependent 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.