Background & Aims: Food additives, such as emulsifiers, stabilizers, or bulking agents, are present in the Western diet and their consumption is increasing. However, little is known about their potential effects on intestinal homeostasis. In this study we examined the effect of some of these food additives on gut inflammation. Methods: Mice were given drinking water containing maltodextrin (MDX), propylene glycol, or animal gelatin, and then challenged with dextran sulfate sodium or indomethacin. In parallel, mice fed a MDX-enriched diet were given the endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA). Transcriptomic analysis, real-time polymerase chain reaction, mucin-2 expression, phosphorylated p38 mitogen-activated protein (MAP) kinase quantification, and H&E staining was performed on colonic tissues. Mucosa-associated microbiota composition was characterized by 16S ribosomal RNA sequencing. For the in vitro experiments, murine intestinal crypts and the human mucus-secreting HT29-methotrexate treated cell line were stimulated with MDX in the presence or absence of TUDCA or a p38 MAP kinase inhibitor. Results: Diets enriched in MDX, but not propylene glycol or animal gelatin, exacerbated intestinal inflammation in both models. Analysis of the mechanisms underlying the detrimental effect of MDX showed up-regulation of inositol requiring protein 1β a sensor of ER stress, in goblet cells, and a reduction of mucin-2 expression with no significant change in mucosa-associated microbiota. Stimulation of murine intestinal crypts and HT29-methotrexate treated cell line cells with MDX induced inositol requiring protein 1β via a p38 MAP kinase–dependent mechanism. Treatment of mice with TUDCA prevented mucin-2 depletion and attenuated colitis in MDX-fed mice. Conclusions: MDX increases ER stress in gut epithelial cells with the downstream effect of reducing mucus production and enhancing colitis susceptibility.
The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress–Driven Mucus Depletion and Exacerbates Intestinal Inflammation / F. Laudisi, D. Di Fusco, V. Dinallo, C. Stolfi, A. Di Grazia, I. Marafini, A. Colantoni, A. Ortenzi, C. Alteri, F. Guerrieri, M. Mavilio, F. Ceccherini-Silberstein, M. Federici, T.T. Macdonald, I. Monteleone, G. Monteleone. - In: CMGH. - ISSN 2352-345X. - 7:2(2019 Jan 01), pp. 457-473.
|Titolo:||The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress–Driven Mucus Depletion and Exacerbates Intestinal Inflammation|
|Parole Chiave:||Colitis; IBD; Intestinal Epithelium; Unfolded Protein Response; Animals; Cattle; Colitis; Diet; Endoplasmic Reticulum Stress; Epithelial Cells; Food Additives; Gastrointestinal Microbiome; Inflammation; Intestines; Membrane Proteins; Mice, Inbred BALB C; Mucus; Polysaccharides; Protein-Serine-Threonine Kinases; Swine; Unfolded Protein Response; Up-Regulation; p38 Mitogen-Activated Protein Kinases; Disease Progression|
|Settore Scientifico Disciplinare:||Settore MED/07 - Microbiologia e Microbiologia Clinica|
|Data di pubblicazione:||1-gen-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.jcmgh.2018.09.002|
|Appare nelle tipologie:||01 - Articolo su periodico|