When 'E-Additives' Hits the Gut: What a New Review Says About Dyes, Sweeteners, Emulsifiers, and Preservatives

The FASEB Journal has published a major review by Canadian researchers (McMaster University) on how the most common food additives - from artificial colors and non-nutritive sweeteners to emulsifiers and preservatives - interfere with the delicate balance of the intestine. The authors collect data from cellular, animal, and early human studies and show that a number of additives change the composition and function of the microbiota, thin the mucus barrier, disrupt tight junctions of the epithelium, and increase inflammation - especially noticeable in models of inflammatory bowel disease (IBD). Against the background of the lack of nutritional value of many of these components, they call for updated regulatory assessments and larger-scale epidemiological and clinical studies.

Background of the study

Ultra-processed foods have become a permanent part of the diet, and with them, daily exposure to food additives: dyes, non-caloric sweeteners, emulsifiers, preservatives. Historically, their safety has been assessed based on whole-body toxicology and acute effects, while the subtle effects on the gut ecosystem—the microbiota, mucus layer, tight junctions—have long remained out of focus. In recent years, mechanistic evidence has accumulated that a number of common additives can “shake up” gut homeostasis: shifting the composition and function of the microbiota, thinning mucus, increasing permeability, and exacerbating inflammation, especially in susceptible individuals. A new review in The FASEB Journal summarizes these trends and calls for updating regulatory approaches to take into account the impact on the gut.

The most consistent body of evidence concerns emulsifiers. A classic study showed that even low concentrations of carboxymethylcellulose (CMC) and polysorbate 80 (P80) in mice caused bacterial “layering” on the epithelium, altered the composition of the microbiota, and triggered low-grade inflammation and metabolic shifts; in animals prone to colitis, emulsifiers increased intestinal inflammation. These signals are partially confirmed in humans: in a randomized controlled trial, adding CMC to an “unsupplemented diet” increased postprandial discomfort, altered the microbiota, and altered metabolites, indicating disruption of mucosal barrier mechanisms.

Among artificial dyes, the most striking example is Allura Red (E129): in a chronic consumption model, this azo dye increased vulnerability to colitis in mice via increased intestinal serotonin and microbiota-dependent pathways; transfer of microbiota from “exposed” animals increased inflammation in recipients. Although direct human data are still limited, the direction of risk is indicated, and it is discussed in the review paper as potentially significant for people with inflammatory bowel disease.

With non-caloric sweeteners, the picture is more mixed: cohort studies often find unfavorable associations, while RCTs yield mosaic results. A randomized trial in healthy volunteers is indicative: different sweeteners altered the microbiota and glycemic responses in a personalized manner, which hints at a dependence of the effect on the initial microbial profile. Against this background, the WHO issued a cautious recommendation to limit the routine use of NNS, and the FASEB review emphasizes the need for large, standardized trials in humans and a revision of the “default safe” statuses taking into account intestinal outcomes.

Why is this important?

Ultra-processed foods have become the norm in many countries, and daily exposure to synthetic additives is growing with them. The review highlights that they may be the missing link in the “processed food ↔ risk of intestinal disorders” relationship, from IBD flare-ups to functional disorders. In a parallel press commentary, the co-authors note that since additives do not provide nutritional benefits, reducing their share in the diet may be a wise choice, especially for people with a vulnerable gastrointestinal tract.

What happens in the intestines

When we chronically consume products with “E-additives,” a cascade of changes can be triggered in the intestines: microbes shift toward dysbiosis, the mucous film over the epithelium becomes thinner, tight cell junctions “lose,” and the immune system goes into inflammatory mode. The result is increased permeability (“leaky gut”), “allowing” microbial patterns to immune cells, and, in susceptible people, a more severe course of inflammation.

Key groups of additives and what is known about them

• Artificial colors (AFCs): Allura Red (E129), Tartrazine (E102), Sunset Yellow (E110), TiO₂ (E171). In mouse models, Allura Red at doses commensurate with the acceptable daily intake caused low-intensity inflammation and increased colitis; early exposure increased vulnerability in the future. Impaired barrier function (including through MLCK), DNA damage in the colon, and even the role of serotonin as a mediator have been shown. Some studies link Sunset Yellow to activation of the NLRP3 inflammasome (IL-1β, IL-18), dysbiosis, and failures of adhesive contacts. An important detail: microbes are able to reduce azo dyes to metabolites, which trigger inflammation.
• Emulsifiers: carboxymethylcellulose (CMC/E466), polysorbate-80 (P80/E433), carrageenan (E407). Their amphiphilic molecules stabilize products, but experiments regularly show increased inflammation, bacteria convergence with the epithelium, dysbiosis, and thinning of mucus. A particularly robust array of data with the same vector of effects has accumulated for CMC and P80.
• Non-nutritive sweeteners (NNS): saccharin (E954), sucralose (E955), acesulfame-K (E950), neo-/advantame. Studies indicate changes in microbiota and immune circuits; EU regulators regularly review the safety profiles of individual molecules (e.g. saccharin - EFSA re-evaluation in 2024; acesulfame-K - in 2025). Human data are still mixed, but there is a signal of potential disruption of intestinal homeostasis, which requires careful RCTs.
• Preservatives and antioxidants: sulfites, benzoates, nitrites, etc. They are given a smaller share in the review, but the trend is similar: the effect on the barrier and immune response with long-term use, especially against the background of a vulnerable intestine. Here, too, more rigorous studies in humans are needed.

The power of evidence and the weak points

The review is fair in its boundaries: most mechanistic observations come from animal models and cell systems, and in humans, point signals are still demanding in design. However, with the increasing prevalence of IBD and high consumption of processed foods, the scale of the problem seems sufficient to warrant reconsidering “generally recognized as safe” (GRAS) statuses and updating regulations. The point is not that “all supplements are equally harmful,” but that some of them, when taken chronically, can “undermine” intestinal homeostasis, and this needs to be systematically measured in human studies.

How this translates into practice today

If you have a sensitive GI tract or are diagnosed in the IBD/IBS spectrum, a smart strategy is to reduce ultra-processed foods and prioritize simple ingredients. The review and researchers' comments offer a moderate, "anti-panic" checklist:

• Read the labels: fewer items with complex names/E indices, especially emulsifiers (E466, E433, E407), dyes (E102, E110, E129) and some sweeteners (E950, E954, E955).
• The short list rule: the shorter the composition, the better the predictability for the intestines.
• Experiment with substitutions: Try reducing supplements for 2-4 weeks and track your symptoms/well-being (food diary).
• Semantics of “natural ≠ safe”: carrageenan is a “natural” polysaccharide, but in experiments it also gives problematic signals.
• Discuss with your doctor: With IBD, any dietary changes should only be made in conjunction with your treating specialist.

What Science and Regulators Should Do

The authors cite priorities: standardize exposure models, move to dose curves closer to real consumption, and expand human studies - from cross-sections and cohorts to randomized interventions with clinical and microbiome endpoints. Regulators should update assessments for commonly used molecules and take into account combined effects (several additives in one product). A separate layer is risk communication for the population: simple tools for navigating labels and clear recommendations for risk groups.

Short lists for reference

• Where additives most often “live”: sweet sodas and “sports” drinks; desserts and confectionery; ready-made sauces/spreads; sausages and delicacies; “fitness bars” and protein sweets.
• What to look for in the composition (examples): E129, E102, E110 (dyes), E466, E433, E407 (emulsifiers/thickeners), E950, E954, E955 (sweeteners), E220-E228 (sulfites), E211 (sodium benzoate). (Presence in the list does not equal "dangerous" - these are markers for an informed choice.)
• What is especially vulnerable: thin mucus over the epithelium, tight cell contacts (barrier), the balance of microbes and the “conversation” between the microbiota and the immune system.

Conclusion

Not all supplements are the same and not all will have problems. But the "alarm signal" is enough to reduce the excess and improve research standards. The intestine is an ecosystem: the less we destabilize it with "extra" techno-ingredients, the more resilient it is to environmental challenges.

Source: Seto T., Grondin JA, Khan WI Food Additives: Emerging Dietary Roles on Gut Health. The FASEB Journal 39(13):e70810 (July 15, 2025). https://doi.org/10.1096/fj.202500737R