The results of research in mice by scientists at Icahn School of Medicine at Mount Sinai suggest that certain artificial food colorants can cause inflammatory bowel disease when the immune system has become dysregulated. The study found that mice with dysregulated expression of the immune system cytokine IL-23 developed colitis when they consumed food with the artificial food colorants Red 40 and Yellow 6. Development of colitis in the animals also required the presence of commensal bacteria that could metabolize the food dyes. The team claims the study, published in Cell Metabolism, is the first to show the phenomenon, although they acknowledged that it remains unclear whether food colorants might have similar effects in humans.

“The dramatic changes in the concentration of air and water pollutants and the increased use of processed foods and food additives in the human diet in the last century correlate with an increase in the incidence of inflammatory and autoimmune diseases,” said Sergio Lira, MD, PhD, the Leona M. and Harry B. Helmsley Charitable Trust Professor of Immunology at the Precision Immunology Institute at Icahn Mount Sinai. “These environmental changes are thought to contribute to development of these diseases, but relatively little is known about how they do so. We hope this research is a step toward understanding the impact of food colorants on human health.” Lira is senior author of the team’s published paper, which is titled, “Food colorants metabolized by commensal bacteria promote colitis in mice with dysregulated expression of interleukin-23.”

Both genetic predisposition and environmental factors are thought to play a role in IBD development, but while more than 200 loci and genes have been linked with IBD in humans, “… the environmental factors contributing to disease have remained elusive,” the authors explained. In particular, they continued, genetic studies in humans have linked the interleukin (IL)-23 signaling pathway with IBD. In fact, IL-23 is one of the best-studied immune factors contributing to development of IBD, and IL-23 dysregulation is known to be a factor in the development of the condition in humans, the team continued. Medicines that block IL-23 function are also now being used successfully in patients. “ … recent clinical studies show that therapies targeting IL-23 are effective in patients with different forms of IBD, such as Crohn’s disease (CD), and ulcerative colitis (UC),” the team noted.

Changes in the levels of air and water pollutants, and the increased use of processed foods and food additives in the human diet over the last century also correlate with an increase in the incidence of inflammatory and autoimmune diseases, the investigators continued, but how such factors link with disease isn’t understood. “These environmental changes are thought to contribute to development of these diseases, but relatively little is known about how they do so,” Lira and colleagues wrote.

Artificial food colorants were first used at the end of the 19th century, and while they are now highly prevalent in diets worldwide, food colorants haven’t been studied in the context of IBD,” the scientists further pointed out. The colorants Red 40 (also known as Allura Red AC), and Yellow 6, are the most widely used in the world, and are found in many foods, beverages and medicines.

For their reported study, the researchers created different mouse models that conditionally expressed IL-23, or in which IL-23 expression was augmented. To their surprise, they found that mice with the dysregulated immune response did not develop inflammatory bowel disease spontaneously, even though dysregulated IL-23 is a factor in people with the disease. However, when given a diet containing the food dyes Red 40 or Yellow 6, the animals did develop colitis. Conversely, control mice with a normal immune system did not develop IBD when given the food dye-infused diet. “We show here that Red 40 alone does not induce colitis in control mice, but it can trigger severe IBD-like colitis in IL-23-overexpressing mice,” the scientists wrote.

To prove that the food colorant was responsible for the development of IBD in the mice with dysregulated immune systems, the researchers fed the animals diets without the food colorant, but gave them water that did contain it. The disease developed when the mice consumed the colorant, but not otherwise. They replicated the finding across several diets and several food colorants.

Interestingly, induction of colitis was dependent on the presence of commensal bacteria that metabolized Red 40 and Yellow 6, to produce a metabolite, 1-amino-naphthol-6-sulfonate sodium salt. “Our studies reveal that food colorants contribute to development of colitis in conditions characterized by increased IL-23 signaling,” the team concluded. “Disease development in this setting requires commensal bacteria, such as E. faecalis and B. ovatus, to metabolize Red 40 or Yellow 6.”

The researchers plan to investigate exactly how the cytokine IL-23 promotes the development of colitis after food colorant exposure. They also noted limitations of their study, and acknowledged that further studies will be needed to understand the broader impact of food colorants. Nevertheless, the team claimed, “Our findings suggest that specific food colorants are risk factors for experimental IBD in conditions of immune dysregulation … These results may have implications for human health as IL-23 is clearly implicated in development of IBD, and consumption of food colorants such as Red 40 and Yellow 6, is widespread.”

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