title: Commensal gut bacteria modulate phosphorylation-dependent PPARγ transcriptional activity in human intestinal epithelial cells.
abstract: 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.
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Nepelska
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.|Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, ETH Zurich, Switzerland.
authors.forename: Tomas
authors.initials: T
authors.lastname: de Wouters
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Jacouton
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Béguet-Crespel
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lapaque
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.|MGP MetaGenoPolis, INRA, Université Paris-Saclay, 78350 Jouy en Josas, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Doré
authors.affiliation: Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Stockholm, Sweden.
authors.forename: Velmurugesan
authors.initials: V
authors.lastname: Arulampalam
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.|MGP MetaGenoPolis, INRA, Université Paris-Saclay, 78350 Jouy en Josas, France.
authors.forename: Hervé M
authors.initials: HM
authors.lastname: Blottière
mesh_terms: D000075803:Angiopoietin-Like Protein 4 / Q000378:metabolism; D001421:Bacteria, Anaerobic / Q000254:growth & development* / Q000378:metabolism; D002087:Butyrates / Q000378:metabolism; D018929:Cell Culture Techniques; D002460:Cell Line; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000502:physiology*; D000069196:Gastrointestinal Microbiome; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology*; D020935:MAP Kinase Signaling System; D047495:PPAR gamma / Q000378:metabolism*; D000070780:Perilipin-2 / Q000378:metabolism; D010766:Phosphorylation; D011422:Propionates / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D002087:Butyrates; D017077:Culture Media, Conditioned; C000602982:PLIN2 protein, human; D047495:PPAR gamma; D000070780:Perilipin-2; D011422:Propionates