title: Commensal Streptococcus salivarius Modulates PPARγ Transcriptional Activity in Human Intestinal Epithelial Cells.
abstract: The impact of commensal bacteria in eukaryotic transcriptional regulation has increasingly been demonstrated over the last decades. A multitude of studies have shown direct effects of commensal bacteria from local transcriptional activity to systemic impact. The commensal bacterium Streptococcus salivarius is one of the early bacteria colonizing the oral and gut mucosal surfaces. It has been shown to down-regulate nuclear transcription factor (NF-кB) in human intestinal cells, a central regulator of the host mucosal immune system response to the microbiota. In order to evaluate its impact on a further important transcription factor shown to link metabolism and inflammation in the intestine, namely PPARγ (peroxisome proliferator-activated receptor), we used human intestinal epithelial cell-lines engineered to monitor PPARγ transcriptional activity in response to a wide range of S. salivarius strains. We demonstrated that different strains from this bacterial group share the property to inhibit PPARγ activation independently of the ligand used. First attempts to identify the nature of the active compounds showed that it is a low-molecular-weight, DNase-, proteases- and heat-resistant metabolite secreted by S. salivarius strains. Among PPARγ-targeted metabolic genes, I-FABP and Angptl4 expression levels were dramatically reduced in intestinal epithelial cells exposed to S. salivarius supernatant. Both gene products modulate lipid accumulation in cells and down-regulating their expression might consequently affect host health. Our study shows that species belonging to the salivarius group of streptococci impact both host inflammatory and metabolic regulation suggesting a possible role in the host homeostasis and health.
authors.affiliation: INRA, UMR 1319 MICALIS, Domaine de Vilvert, Jouy-en-Josas, France; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Couvigny
authors.affiliation: INRA, UMR 1319 MICALIS, Domaine de Vilvert, Jouy-en-Josas, France; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: Tomas
authors.initials: T
authors.lastname: de Wouters
authors.affiliation: INRA, UMR 1319 MICALIS, Domaine de Vilvert, Jouy-en-Josas, France; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: Ghalia
authors.initials: G
authors.lastname: Kaci
authors.affiliation: INRA, UMR 1319 MICALIS, Domaine de Vilvert, Jouy-en-Josas, France; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Jacouton
authors.affiliation: INRA, UMR 1319 MICALIS, Domaine de Vilvert, Jouy-en-Josas, France; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Delorme
authors.affiliation: INRA, UMR 1319 MICALIS, Domaine de Vilvert, Jouy-en-Josas, France; AgroParisTech, UMR Micalis, Jouy-en-Josas, France; INRA, US 1367 MetaGenoPolis, Jouy-en-Josas, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Doré
authors.affiliation: INRA, UMR 1319 MICALIS, Domaine de Vilvert, Jouy-en-Josas, France; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Renault
authors.affiliation: INRA, UMR 1319 MICALIS, Domaine de Vilvert, Jouy-en-Josas, France; AgroParisTech, UMR Micalis, Jouy-en-Josas, France; INRA, US 1367 MetaGenoPolis, Jouy-en-Josas, France.
authors.forename: Hervé M
authors.initials: HM
authors.lastname: Blottière
authors.affiliation: INRA, UMR 1319 MICALIS, Domaine de Vilvert, Jouy-en-Josas, France; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Guédon
authors.affiliation: INRA, UMR 1319 MICALIS, Domaine de Vilvert, Jouy-en-Josas, France; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lapaque
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000096:biosynthesis / Q000235:genetics; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D019073:HT29 Cells; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D064307:Microbiota / Q000276:immunology; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D013291:Streptococcus / Q000276:immunology / Q000378:metabolism*; D013559:Symbiosis; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma