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Title:
Commensal gut bacteria modulate phosphorylation-dependent PPARγ transcriptional activity in human intestinal epithelial cells | Scientific Reports
Description:
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.
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Keywords {🔍}
pparγ, pubmed, activation, article, google, scholar, cas, cells, butyrate, cms, cell, parvulum, copri, gut, intestinal, bacteria, fig, human, propionate, activity, reporter, phosphorylation, microbiota, bacterial, nature, control, central, media, epithelial, kda, commensal, culture, size, activating, medium, transcriptional, expression, concentrations, angptl, effect, observed, cluster, data, nuclear, erk, compounds, analysis, receptor, conditioned, protein,
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nature portfolio privacy policy careful editing pj3-tk-luc advertising extracellular signal-regulated kinases portal 0/ reprints pparγ-dependent luciferase activity nature nature 283 nature 500 nature 491 pparγ-dependent transcriptional activity quantitative real-time pcr development high-fat diet feeding pparγ-dependent reporter cells pparγ-dependent transcriptional response post-hoc tuckey test jun nh2-terminal kinase tauro-beta-muricholic acid diet-induced obesity ht-29-pparγ reporter cells51 author correspondence regulating nuclear-cytoplasmic shuttling monoclonal anti-gapdh-peroxidase modulate pparγ activity ht-29-pparγ reporter cells reporter cell lines luciferase reporter assay dose-dependent activation potential copri -induced signal peroxisomal β-oxidation pathway full size image monte-carlo significance test cellular assay revealed permissions host-microbial interactions shape nf-κb modulation capabilities reporter cell line dose-dependent manner grant agreement health-f4-2007-201052 adipose differentiation-related protein patho-physiological conditions linked oas influencing pparγ-activation pparγ-specific ligand troglitazone pparγ reporter activity lower luciferase activity pparγ transcriptional activity
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- The immune system and the gut microbiota: friends or foes?
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headline:Commensal gut bacteria modulate phosphorylation-dependent PPARγ transcriptional activity in human intestinal epithelial cells
description:In healthy subjects, the intestinal microbiota interacts with the hostâs 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 hostâs health through transcriptional regulation.
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headline:Commensal gut bacteria modulate phosphorylation-dependent PPARγ transcriptional activity in human intestinal epithelial cells
description:In healthy subjects, the intestinal microbiota interacts with the hostâs 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 hostâs health through transcriptional regulation.
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