Maltodextrin Consumption Impairs the Intestinal Mucus Barrier and Accelerates Colitis Through Direct Actions on the Epithelium

Abstract

Food additives are common components of processed foods consumed in a Western diet. In inflammatory bowel disease patients, some diets that exclude food additives improved clinical disease parameters, suggesting a link between food additives and disease pathogenesis. Food additives also enhanced disease severity in mouse colitis models through incompletely described mechanisms. This study examined the mechanisms by which the food additive maltodextrin (MDX) alters the development of colitis in a murine model. Interleukin-10 knockout (IL10KO) mice were fed diets supplemented with MDX or carboxymethyl cellulose (CMC) to determine their impact on colitis onset and severity; microbiome composition, function, and location; colonic immune cell infiltrates; and mucus layer integrity. Primary IL10KO colonic epithelial monolayers were used to dissect the impact of MDX directly on epithelial differentiation and mucus production. MDX or CMC consumption increased the incidence and severity of colitis, as well as decreased microbiome diversity, altered microbial composition, and decreased fecal acetic acid levels. The number of mucus producing cells were decreased in food additive fed mice and resulted in increased microbial proximity to the intestinal epithelium. Additionally, MDX supplementation resulted in crypt hyperplasia and expansion of the HopX+ injury renewal stem cell niche. In primary intestinal epithelial-derived monolayers devoid of microbes and immune cells, MDX exposure decreased goblet cell number and mucus production in association with downregulated expression of the transcription factor Klf4, a marker of terminally differentiated goblet cells. These results suggest MDX disrupts the balance of epithelial cell differentiation and proliferation to contribute to disease pathogenesis through direct and indirect actions on the intestinal epithelial barrier.

Mechanisms of gut epithelial barrier impairment caused by food emulsifiers polysorbate 20 and polysorbate 80

“…The levels of flagellin and LPS were enhanced after treatment with emulsifiers. Metagenomics results have demonstrated an enrichment of genes related to flagella and bacterial motility in the gut microbiome 59,62 . Research conducted on mice has also shown that the consumption of emulsifiers can alter the composition of the gut microbiota, increase intestinal inflammation, and promote metabolic disorders 19 .…”

Pervasive selective sweeps across human gut microbiomes

“…In particular, we saw that genes related to the metabolism maltodextrin—a synthetic starch which has increased dramatically in abundance in Western diets in recent years [59, 60]—appeared to be under selection in several species. As consumption of maltodextrin has been implicated experimentally in the onset of colitis [61, 62], these selective sweeps may have implications for human health. More broadly, future work in which systematic scans of adaptation are performed in a variety of cohorts may reveal genetic loci in the microbiome that are especially relevant to certain human conditions.…”

Intestinal mucosal microbiota mediate amino acid metabolism involved in the gastrointestinal adaptability to cold and humid environmental stress in mice

“…Recent researchers have found that factors that affect the intestinal mucus barrier, such as food intake [26,27], in ammatory bowel diseases (IBDs) [28,29], and Helicobacter pylori infection [30], are key determinants of microbiome composition, therefore directly in uence host GI health, and has been reviewed extensively elsewhere. However, environmental factors known to in uence the intestinal mucus barrier have been comparatively neglected in the microbiome eld.…”