Chronic exposure to synthetic food dye Allura Red AC promotes susceptibility to experimental colitis via intestinal serotonin in mice
Summary Chemicals in food are widely used and lead to significant human exposure. Allura Red AC (AR) is a very common synthetic dye; however, little is known about its impact on colitis. Here, we show that chronic RA exposure at a dose found in commonly consumed dietary products exacerbates experimental mouse models of colitis. Although intermittent exposure is more similar to a typical human exposure, intermittent exposure to RA in mice for 12 weeks does not influence susceptibility to colitis. However, exposure to RA during early life primes mice for increased susceptibility to colitis. Furthermore, chronic RA exposure induces mild colitis, which is associated with elevated colonic serotonin (5-hydroxytryptamine; 5-HT) levels and impairment of epithelial barrier function through myosin light chain kinase (MLCK). . Importantly, chronic RA exposure does not influence colitis susceptibility in mice lacking tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme for 5-HT biosynthesis. Cecal transfer of gut microbiota perturbed by RA exposure worsens colitis severity in recipient germ-free (GF) mice. Furthermore, chronic RA exposure elevates colonic 5-HT levels in naïve GF mice. Although it is still unknown whether AR has similar effects in humans, our study reveals that long-term chronic exposure to a common synthetic dye promotes experimental colitis via colonic 5-HT-dependent and gut microbiota-independent pathway in mice. |
Graphical summary showing the effect of RA on the development of colitis. AR disrupts the integrity of the intestinal epithelial barrier through MLCK and the mucus layer, while AR also stimulates colonic secretion of 5-HT, modulates the composition of the intestinal microbiota, and promotes colitis. Under GF conditions, AR also induces colonic secretion of 5-HT, which primes for inflammatory reactions.
Comments
Researchers using experimental animal models of IBD found that continued exposure to Allura Red AC harms gut health and promotes inflammation. The dye directly disrupts intestinal barrier function and increases the production of serotonin, a hormone/neurotransmitter found in the intestine, which subsequently alters the composition of the intestinal microbiota and increases susceptibility to colitis. The study suggests a link between a commonly used food dye and IBD and warrants further exploration between food dyes and IBD at experimental, epidemiological, and clinical levels.
Long-term consumption of Allura Red food dye may be a potential trigger for inflammatory bowel diseases (IBD), Crohn’s disease, and ulcerative colitis, says Waliul Khan of McMaster University. Researchers using experimental animal models of IBD found that continued exposure to Allura Red AC harms gut health and promotes inflammation.
The dye directly disrupts intestinal barrier function and increases the production of serotonin , a hormone/neurotransmitter found in the intestine, which subsequently alters the composition of the intestinal microbiota and increases susceptibility to colitis.
Khan said Allura Red (also called FD&C Red 40 and Food Red 17), is a common ingredient in candy, soft drinks, dairy products and some cereals. Dye is used to add color and texture to foods, often to appeal to children.
The use of synthetic food dyes like Allura Red has increased significantly in recent decades, but there have been few previous studies on the effects of these dyes on gut health. Khan and his team published their findings in Nature Communications. Yun Han (Eric) Kwon, who recently completed his PhD in Khan’s lab, is the first author.
"This study demonstrates significant harmful effects of Allura Red on intestinal health and identifies intestinal serotonin as a critical factor mediating these effects. These findings have an important implication in the prevention and management of intestinal inflammation," Khan said. , senior author of the study, professor in the Department of Pathology and Molecular Medicine and principal investigator at the Farncombe Family Digestive Health Research Institute.
"What we have found is surprising and alarming, as this common synthetic food dye is a possible dietary trigger of IBD.
"This research is a significant step forward in alerting the public to the potential harms of the food dyes we consume every day," he said.
"Literature suggests that Allura Red consumption also affects certain allergies, immune disorders, and behavioral problems in children, such as attention deficit hyperactivity disorder."
Khan said IBDs are serious chronic inflammatory conditions of the human intestine that affect millions of people around the world. While their exact causes are not yet fully understood, studies have shown that dysregulated immune responses, genetic factors, gut microbiota imbalances, and environmental factors can trigger these conditions.
In recent years there has been significant progress in the identification of susceptibility genes and understanding the role of the immune system and host microbiota in the pathogenesis of IBD. However, similar advances in defining environmental risk factors have lagged, he said.
Khan said environmental triggers for IBD include the typical Western diet, which includes processed fats, red and processed meats, sugar and a lack of fiber. He added that the Western diet and processed foods also include large amounts of various additives and colorings.
He added that the study suggests a link between a commonly used food dye and IBD and warrants further exploration between food dyes and IBD at the experimental, epidemiological and clinical levels.
Final message
Collectively, we show that chronic, but not intermittent, exposure to RA increases susceptibility to colitis, and that colonic 5-HT is a key mediator for the phenotype observed in mice. As our knowledge of the associations between perturbed gut microbiota and IBD increases, the effects of environmental factors, such as diet, are increasingly becoming a public health concern. Our findings provide important data on the potential role of AR in promoting murine colitis and warrant further investigations into the role of other commonly used food dyes, such as BB, SY, and TY, in the pathogenesis of colitis. Additionally, future studies are needed to identify similar effects in humans. Therefore, this study will not only drive scrutiny of its use in many industries, but also promote public awareness to prevent adverse health consequences.
The study was funded by the Canadian Institutes of Health Research.
