When the immune system is dysregulated, food dyes cause colitis

Scientists at Mount Sinai's Icahn School of Medicine have discovered that some artificial food colors may induce inflammatory bowel disease in mice when the immune system is dysregulated. When mice with dysregulated expression of the immune system cytokine IL-23 ate food containing the artificial food colors Red 40 and Yellow 6, they developed colitis, according to the report. The existence of commensal bacteria that could metabolize the food dyes was also needed for the development of colitis in the animals. The researchers say that their analysis, which was published in Cell Metabolism, is the first to demonstrate the phenomenon, though they admit that it's unclear if food dyes have similar effects in humans.

“In the last century, dramatic changes in the concentration of air and water pollutants, as well as increased use of processed foods and food additives in the human diet, have all been linked to 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 IUPUI. “These changes in the climate are believed to play a role in the development of these diseases, but little is understood about how they do so. We hope that this study will help us better understand the effects of food dyes on human health.” Lira is a senior author on the team's recently published article, titled, “Food colorants metabolized by commensal bacteria promote colitis in mice with dysregulated expression of interleukin-23.”

Although more than 200 loci and genes have been linked to IBD in humans, the authors clarified that “the environmental factors leading to disease have remained elusive.” They went on to say that human genetic studies have related the interleukin (IL)-23 signaling pathway to IBD. In reality, IL-23 is one of the most well-studied immune factors involved in the development of IBD, and IL-23 dysregulation is known to play a role in the progression of the disease in humans, according to the researchers. Medicines that inhibit the action of IL-23 are now being successfully used in patients. “Recent clinical trials indicate that therapies targeting IL-23 are successful in patients with various types of IBD, such as Crohn's disease (CD) and ulcerative colitis (UC),” the researchers wrote.

Changes in air and water pollution levels, as well as increased use of processed foods and food additives in the human diet, have all been linked to a rise in the incidence of inflammatory and autoimmune diseases over the last century, according to the researchers, but how these factors lead to disease is unknown. “Such environmental changes are thought to lead to the emergence of these diseases,” Lira and colleagues wrote, “but very little is understood about how they do so.”

Artificial food colorants were first used at the end of the nineteenth century, and although they are now widely used in diets around the world, they have yet to be studied in the sense of IBD, according to the researchers. The most commonly used colorants in the world are Red 40 (also known as Allura Red AC) and Yellow 6, which can be found in a variety of foods, drinks, and medicines.

The researchers developed different mouse models that conditionally expressed IL-23 or augmented IL-23 expression for their published analysis. Even though dysregulated IL-23 is a factor in people with the disease, they were surprised to find that mice with the dysregulated immune response did not develop inflammatory bowel disease spontaneously. The animals did develop colitis when fed a diet containing the food dyes Red 40 or Yellow 6. Control mice with a healthy immune system, on the other hand, did not grow IBD when fed the food dye-infused diet. The researchers wrote, “We show here that although Red 40 alone does not cause colitis in control mice, it can cause serious IBD-like colitis in IL-23-overexpressing mice.”

The researchers fed the mice diets without the food colorant but gave them water that did contain it to show that the food colorant was responsible for the production of IBD in mice with dysregulated immune systems. When the mice ate the colorant, they got sick, but they didn't get sick otherwise. They were able to replicate the findings through a variety of diets and food colorants.

Surprisingly, the presence of commensal bacteria that metabolized Red 40 and Yellow 6 to produce a metabolite, 1-amino-naphthol-6-sulfonate sodium salt, was needed for the induction of colitis. The researchers concluded, "Our studies show that food colorants lead to the development of colitis in conditions characterized by enhanced IL-23 signaling." “In this setting, disease production necessitates the metabolization of Red 40 or Yellow 6 by commensal bacteria such as E. faecalis and B. ovatus.”

The researchers want to learn more about how the cytokine IL-23 facilitates the production of colitis in people who have been exposed to food dyes. They also recognized that their study had limitations and that further research is required to understand the wider effect of food colorants. “Our results indicate that unique food colorants are risk factors for experimental IBD in conditions of immune dysregulation,” the team concluded. Since IL-23 is specifically linked to the production of IBD, and food colorants like Red 40 and Yellow 6 are widely consumed, these findings may have consequences for human health.”