The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress–Driven Mucus Depletion and Exacerbates Intestinal Inflammation

Abstract

Background & AimsFood 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.MethodsMice 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.ResultsDiets 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.ConclusionsMDX increases ER stress in gut epithelial cells with the downstream effect of reducing mucus production and enhancing colitis susceptibility.

Maltodextrin-induced intestinal injury in a neonatal mouse model

“…The maltodextrin-dominant formula-induced intestinal injury mouse model also demonstrated a differential risk based on postnatal age and thus provides a basis for understanding developmental vulnerability for intestinal damage. The impact of maltodextrin is likely to be multifactorial, with epithelial cell-driven mechanisms, but the carbohydrate likely also alters the microbial phenotype and gut inflammation (Laudisi et al, 2019;Nickerson et al, 2015). In addition to epithelium-dependent pathways, immature gut microcirculation and reduced postprandial hyperemia may be an important factor leading to intestinal injury in younger, immature mice versus older, more mature mice (Chen et al, 2019).…”

The Role of the Gut Microbiota in Dietary Interventions for Depression and Anxiety

“…Salt is another food additive that tends to be in high concentration in processed foods and Seck et al ( 235 ) found that high fecal salinity alters gut microbe composition, including a decrease in the beneficial bacteria Akkermansia muciniphila and Bifidobacterium spp., specifically B. longum and B. adolescentis . Maltodextrin reduces mucus production and increases gut inflammation by increasing endoplasmic reticulum stress ( 236 ). The links between a Western diet and depression may include an effect of food additives on the gut microbiota.…”

Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes

“…Additionally, the food additive titanium dioxide, commonly used as a whitening and brightening agent, promotes colon inflammation and neoplastic lesions in chemically-induced carcinogenesis models [ 76 , 77 ]. Relatively low concentrations of two commonly used emulsifiers, carboxymethylcellulose and polysorbate-80, altered the gut microbiota composition and promoted low-grade intestinal inflammation in animal models [ 78 , 79 ]. These data suggest a role of food additives in the incidence of CRC development in humans.…”