Commensal gut bacteria modulate phosphorylation-dependent PPARγ transcriptional activity in human intestinal epithelial cells.
Commensal gut bacteria modulate phosphorylation-dependent PPARγ transcriptional activity in human intestinal epithelial cells.
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DOI：
10.1038/srep43199
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发表时间：
2017-03-07
影响因子：
4.6
通讯作者：
Blottière HM
中科院分区：
文献类型：
--
作者：
Nepelska M;de Wouters T;Jacouton E;Béguet-Crespel F;Lapaque N;Doré J;Arulampalam V;Blottière HM
在健康受试者中，肠道微生物群与宿主的上皮相互作用，调节基因表达，使宿主和微生物群都受益。然而，对潜在的机制仍然知之甚少。虽然许多肠道细菌尚未培养，但已经建立了不断增长的培养物收藏。我们选择了57种代表性的肠道细菌菌株来研究细菌-宿主相互作用，重点是PPARγ，这是结肠细胞中将代谢和炎症与微生物群联系起来的关键核受体。从厌氧培养物中收获条件培养基（CM），并使用报告细胞系评估其调节PPARγ的能力。PPARγ转录活性的激活与丁酸盐和丙酸盐的存在有关，丁酸盐和丙酸盐是肠道细菌的两种主要代谢物。有趣的是，一些刺激性CM缺乏这些代谢物。选择一株普雷沃氏菌和一株Atopobium菌株进行进一步研究，并显示上调两个PPARγ靶基因ANGPTL 4和ADRP。这些激活的分子机制涉及通过ERK 1/2磷酸化PPARγ。负责的代谢产物被证明是热敏感的，但在大小上明显不同，强调了在肠道中发现的生物活性化合物的多样性。在这里，我们描述了不同的机制，通过这些机制，单个肠道细菌可以通过转录调控直接影响宿主的健康。
In healthy subjects, the intestinal microbiota interacts with the host’s epithelium, regulating gene expression to the benefit of both, host and microbiota. The underlying mechanisms remain poorly understood, however. Although many gut bacteria are not yet cultured, constantly growing culture collections have been established. We selected 57 representative commensal bacterial strains to study bacteria-host interactions, focusing on PPARγ, a key nuclear receptor in colonocytes linking metabolism and inflammation to the microbiota. Conditioned media (CM) were harvested from anaerobic cultures and assessed for their ability to modulate PPARγ using a reporter cell line. Activation of PPARγ transcriptional activity was linked to the presence of butyrate and propionate, two of the main metabolites of intestinal bacteria. Interestingly, some stimulatory CMs were devoid of these metabolites. A Prevotella and an Atopobium strain were chosen for further study, and shown to up-regulate two PPARγ-target genes, ANGPTL4 and ADRP. The molecular mechanisms of these activations involved the phosphorylation of PPARγ through ERK1/2. The responsible metabolites were shown to be heat sensitive but markedly diverged in size, emphasizing the diversity of bioactive compounds found in the intestine. Here we describe different mechanisms by which single intestinal bacteria can directly impact their host’s health through transcriptional regulation.