From the Journals

Maltodextrin may increase colitis risk

Maltodextrin is a polysaccharide derived from starch hydrolysis and broadly used as a thickener and filler in processed food. While it is regarded as inert and considered “generally regarded as safe” by the U.S. Food and Drug Administration, multiple recent studies have demonstrated detrimental roles played by maltodextrin in the intestinal environment, suggesting that this broadly used food additive may play a role in chronic inflammatory diseases.

Dr. Benoit Chassaing is an assistant professor in the Neuroscience Institute and Institute for Biomedical Sciences, Georgia State University, Atlanta.

Dr. Benoit Chassaing

This study by Laudisi et al. added a new line to this list of evidence. Using two different models of colitis, the authors found that consumption of maltodextrin exacerbated intestinal inflammation. Mechanistically, such detrimental effects of maltodextrin were linked to activation of endoplasmic reticulum stress and subsequent alterations of the protective mucus layer.

Importantly, in addition to the use of a murine model of colitis, Laudisi and colleagues also investigated the impact that maltodextrin may have on a “normal” host, i.e. without genetic susceptibility nor induced colitis. While maltodextrin did not induce visible levels of intestinal inflammation, it led to the development of low-grade intestinal inflammation, characterized by subtle but nonetheless consistent elevation in intestinal inflammatory markers, ultimately leading to metabolic abnormalities.

Altogether, these recent results, together with previous reports, suggest that consumption of the food additive maltodextrin may be a risk factor for the IBD-prone population, as well as a factor promoting chronic low-grade intestinal inflammation leading to metabolic abnormalities in the general population. These findings further support the concept that FDA testing of food additives should be performed in disease-prone and resistant host models, designed to detect chronic and low-grade inflammation, as well as consider impacts on the gut microbiota.

Benoit Chassaing, PhD, is an assistant professor in the Neuroscience Institute and Institute for Biomedical Sciences, Georgia State University, Atlanta. He has no conflicts. These remarks are excerpted from an editorial accompanying Dr. Laudisi’s article (CMGH. 2019 Jan 18.



The food additive maltodextrin may increase risk of inflammatory bowel disease, according to a recent study.

Compared with control subjects, mice given drinking water that contained 5% maltodextrin were significantly more likely to develop colitis and lose weight when challenged with dextran sodium sulfate (DSS), reported lead author Federica Laudisi, PhD, of the department of systems medicine at the University of Rome Tor Vergata in Rome, and her colleagues.

Further experiments with murine intestinal crypts and a human cell line echoed these results and offered mechanistic insight. Treatment with maltodextrin stressed the endoplasmic reticulum of goblet cells, predisposing the intestinal epithelium to mucus depletion and inflammation. With these results, maltodextrin joins polysorbate 80 and carboxymethylcellulose on a growing list of food additives in the Western diet with proinflammatory potential.

“Although the U.S. Food and Drug Administration recognizes these dietary elements as safe,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology, “their use has been linked to the development of intestinal pathologies in both animals and human beings.

“It also has been shown that the polysaccharide maltodextrin, which is commonly used as a filler and thickener during food processing, can alter microbial phenotype and host antibacterial defenses. Maltodextrin expands the Escherichia coli population in the ileum and induces necrotizing enterocolitis in preterm piglets (Am J Physiol Gastrointest Liver Physiol. 2009 Dec;297:G1115-25).”

The present study began by administering three compounds dissolved in drinking water to wild-type Balb/c mice for 45 days: 5% maltodextrin, 0.5% propylene glycol, or 5 g/L animal gelatin. Control mice drank plain water. None of the treatments triggered clinical or histologic signs of colitis, and stool levels of lipocalin-2 (Lcn-2), a biomarker of intestinal inflammation, remained comparable with that of control mice. However, outcomes changed when mice were challenged with DSS (1.75% in drinking water) on days 35-45 or injected subcutaneously with indomethacin (5 mg/kg) on day 35 and sacrificed 24 hours later. When challenged with DSS, mice in the maltodextrin group developed severe colitis and lost 10%-15% of body weight, compared with minimal colitis and negligible weight loss in the other groups. In addition, compared with other mice, maltodextrin-fed mice had increased colon tissue expression of Lcn-2 and inflammatory cytokine interleukin (IL)-1beta. These initial findings suggested that dietary maltodextrin could increase susceptibility to clinical colitis.

To determine the pathophysiology of this phenomenon, the investigators performed microarray analysis of colonic samples. Multiple genes associated with carbohydrate and lipid metabolism were upregulated in maltodextrin-fed mice, including genes that controlled the unfolded protein response (UPR), a process in which unfolded proteins accumulate in the endoplasmic reticulum (ER) during ER stress. The most prominently expressed among the UPR-related genes was Ern-2, which regulates inositol-requiring enzyme 1beta, found exclusively in the ER of goblet cells in the small intestine and colon. When maltodextrin causes ER stress in goblet cells, it leads to misfolding of mucin glycoprotein Mucin-2 (Muc-2), a major component of gut mucus, causing gut mucus levels to drop. A diminished mucus barrier exposes the intestine to infection and damage, as demonstrated by higher rates of pathogenic bacteria in Muc-2–deficient mice than in control mice, and more severe intestinal damage than in controls when Muc-2 mice are deliberately infected with pathogens.

The investigators found that humans likely have similar responses to dietary maltodextrin. Treating the mucus-secreting HT29-methotrexate treated (HT29-MTX) cell line with 5% maltodextrin resulted in upregulation of Ern-2, which is the same mechanism observed in mice. Additional testing showed that this process was mediated by p38 mitogen-activated protein kinase, and pharmacologic inhibition or knockdown of p38 suppressed RNA expression of Ern-2. The investigators found that p38 was similarly involved in maltodextrin-fed mice.

To show that maltodextrin enhances susceptibility to inflammation via ER stress, the investigators used tauroursodeoxycholic acid (TUDCA) to inhibit ER stress. Indeed, inhibition led to reduced Ern-2 expression in HT29-MTX cells and in mice treated with maltodextrin. Giving TUDCA to maltodextrin-fed mice resulted in less weight loss, improved histology, and lower expression of Lcn-2 and IL-1beta.

The study concluded with three final experiments: The first showed that maltodextrin did not alter mucosa-associated microbiota; the second showed that mice fed 5% maltodextrin long term (for 10 weeks) had low-grade intestinal inflammation on histology, albeit without clinical colitis or weight loss; and the third showed that mice consuming maltodextrin long term had higher 15-hour fasting blood glycemic levels than control mice, supporting recent research suggesting that food additives can disrupt metabolism in a nonsusceptible host.

“In conclusion,” the investigators wrote, “this study shows that a maltodextrin-enriched diet reduces the intestinal content of Muc-2, thus making the host more sensitive to colitogenic stimuli. These data, together with the demonstration that maltodextrin can promote epithelial intestinal adhesion of pathogenic bacteria, supports the hypothesis that Western diets rich in maltodextrin can contribute to gut disease susceptibility.”

The study was funded by the Italian Ministry of Education, Universities, and Research. The authors reported no conflicts of interest.

SOURCE: Laudisi F et al. CMGH. 2019 Jan 18. doi: 10.1016/j.jcmgh.2018.09.002.

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