PRJNA483554
The food additive maltodextrin promotes endoplasmic reticulum stress-driven mucus depletion and exacerbates intestinal inflammation
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. Maltodextrin (MDX)-enriched diet exacerbated intestinal inflammation in experimental models of colitis and ileitis. Analysis of the mechanisms underlying the detrimental effect of MDX revealed up-regulation of the inositol-requiring enzyme (IRE)1ß, a sensor of endoplasmic reticulum (ER) stress, in goblet cells and reduction of mucin-2 expression with no significant change in mucosa-associated microbiota composition. Stimulation of murine intestinal crypts and the human mucus-secreting cells with MDX induced IRE1ß via a p38 MAP kinase-dependent mechanism. Treatment of mice with the ER stress inhibitor Tauroursodeoxycholic acid prevented mucin-2 depletion and attenuated colitis in MDX-fed mice. Interestingly, mice receiving a prolonged MDX-enriched diet exhibited low-grade intestinal inflammation, which was characterized by focal inflammatory infiltrates, distortion of gland architecture and edema.In conclusion, this study shows, for the first time, that MDX-enriched diet triggers ER stress in goblet cells with consequent reduction of the intestinal content of mucin-2, thus making the host more sensitive to colitogenic stimuli. Our data supports the hypothesis that western diet rich in the food additive MDX can contribute to gut disease susceptibility.