The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress-Driven Mucus Depletion and Exacerbates Intestinal Inflammation.
Animals
Cattle
Colitis
/ microbiology
Diet
Disease Progression
Endoplasmic Reticulum Stress
/ drug effects
Epithelial Cells
/ drug effects
Food Additives
/ adverse effects
Gastrointestinal Microbiome
Inflammation
/ microbiology
Intestines
/ microbiology
Membrane Proteins
/ metabolism
Mice, Inbred BALB C
Mucus
/ metabolism
Polysaccharides
/ adverse effects
Protein Serine-Threonine Kinases
/ metabolism
Swine
Unfolded Protein Response
/ drug effects
Up-Regulation
/ drug effects
p38 Mitogen-Activated Protein Kinases
/ metabolism
Colitis
IBD
Intestinal Epithelium
Unfolded Protein Response
Journal
Cellular and molecular gastroenterology and hepatology
ISSN: 2352-345X
Titre abrégé: Cell Mol Gastroenterol Hepatol
Pays: United States
ID NLM: 101648302
Informations de publication
Date de publication:
2019
2019
Historique:
received:
06
03
2018
revised:
27
08
2018
accepted:
04
09
2018
pubmed:
16
2
2019
medline:
7
5
2019
entrez:
16
2
2019
Statut:
ppublish
Résumé
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. 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. 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. MDX increases ER stress in gut epithelial cells with the downstream effect of reducing mucus production and enhancing colitis susceptibility.
Sections du résumé
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.
Identifiants
pubmed: 30765332
pii: S2352-345X(18)30121-8
doi: 10.1016/j.jcmgh.2018.09.002
pmc: PMC6369223
pii:
doi:
Substances chimiques
Food Additives
0
Membrane Proteins
0
Polysaccharides
0
maltodextrin
7CVR7L4A2D
Ern2 protein, mouse
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
457-473Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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