Dietary Emulsifiers Directly Impact Adherent-Invasive E. coli Gene Expression to Drive Chronic Intestinal Inflammation
Emilie Viennois,
Alexis Bretin,
Philip E. Dubé,
Alexander C. Maue,
Charlène J.G. Dauriat,
Nicolas Barnich,
Andrew T. Gewirtz,
Benoit Chassaing
Affiliations
Emilie Viennois
INSERM, U1149, Center of Research on Inflammation, Université de Paris, Paris, France; Institute for Biomedical Sciences, Center for Inflammation, Immunity and Infection, Digestive Disease Research Group, Georgia State University, Atlanta, GA, USA
Alexis Bretin
Institute for Biomedical Sciences, Center for Inflammation, Immunity and Infection, Digestive Disease Research Group, Georgia State University, Atlanta, GA, USA
Philip E. Dubé
Taconic Biosciences Inc, Rensselaer, NY, USA
Alexander C. Maue
Taconic Biosciences Inc, Rensselaer, NY, USA
Charlène J.G. Dauriat
INSERM U1016, team “Mucosal microbiota in chronic inflammatory diseases”, CNRS UMR 8104, Université de Paris, Paris, France
Nicolas Barnich
Université Clermont Auvergne/Inserm U1071 USC-INRA 2018, Microbes, Intestin, Inflammation et Susceptibilité de l’Hôte (M2iSH), Clermont-Ferrand, France
Andrew T. Gewirtz
Institute for Biomedical Sciences, Center for Inflammation, Immunity and Infection, Digestive Disease Research Group, Georgia State University, Atlanta, GA, USA
Benoit Chassaing
Institute for Biomedical Sciences, Center for Inflammation, Immunity and Infection, Digestive Disease Research Group, Georgia State University, Atlanta, GA, USA; INSERM U1016, team “Mucosal microbiota in chronic inflammatory diseases”, CNRS UMR 8104, Université de Paris, Paris, France; Neuroscience Institute, Georgia State University, Atlanta, GA, USA; Corresponding author
Summary: Dietary emulsifiers carboxymethylcellulose (CMC) and polysorbate-80 (P80) disturb gut microbiota, promoting chronic inflammation. Mice with minimal microbiota are protected against emulsifiers’ effects, leading us to hypothesize that these compounds might provoke select pathobionts to promote inflammation. Gnotobiotic wild-type (WT) and interleukin-10 (IL-10)−/− mice were colonized with Crohn’s-disease-associated adherent-invasive E. coli (AIEC) and subsequently administered CMC or P80. AIEC colonization of GF and altered Schaedler flora (ASF) mice results in chronic intestinal inflammation and metabolism dysregulations when consuming the emulsifier. In IL-10−/− mice, AIEC mono-colonization results in severe intestinal inflammation in response to emulsifiers. Exposure of AIEC to emulsifiers in vitro increases its motility and ability to adhere to intestinal epithelial cells. Transcriptomic analysis reveals that emulsifiers directly induce expression of clusters of genes that mediate AIEC virulence and promotion of inflammation. To conclude, emulsifiers promote virulence and encroachment of pathobionts, providing a means by which these compounds may drive inflammation in hosts carrying such bacteria.
