Both emulsifiers caused dose-dependent damage to intestinal cells and impaired the epithelial barrier, the layer of cells that separates the contents of the intestine from underlying tissues. An intact intestinal barrier helps control which substances cross from the gut into the body and limits exposure of the immune system to microbes and other materials in the intestinal contents.

In gut-on-a-chip experiments, soy lecithin caused significant barrier impairment at concentrations four to 16 times lower than the concentration at which overt toxic effects on the cells were observed. DATEM similarly impaired barrier integrity at concentrations four to 16 times lower than its cytotoxic concentration. The findings were replicated in human colon organoid-on-a-chip models.

The researchers also found that both emulsifiers disrupted the organization of ZO-1, a protein associated with the tight junctions that help seal neighboring intestinal cells together. Changes were observed even at relatively low tested concentrations, providing additional evidence of weakened intestinal barrier integrity.

The study noted that reported use levels ranged from 10–50 milligrams per kilogram (mg/kg) for lecithin and 5–56 mg/kg for DATEM across foods including nut spreads, cocoa and chocolate products, confectionery, bread and rolls, processed meats, food supplements, and chewing gum. The researchers also pointed to the use of the “quantum satis” principle, under which there is no specified maximum permitted level and an additive is used at an amount sufficient to achieve its intended purpose.

Emulsifiers Triggered Inflammation and Cellular Stress

Analyses of gene and protein activity showed that both emulsifiers activated biological pathways associated with inflammation, cellular stress, and cell death, although the researchers found differences in how the two additives produced these effects.

Soy lecithin activated inflammatory pathways involving TNF and NF-κB, which are important regulators of the body's inflammatory response. It also caused oxidative stress, a condition in which reactive oxygen molecules can damage cells, at concentrations below those associated with overt cell toxicity. Treatment with an antioxidant reduced the production of several inflammatory mediators but did not restore the intestinal barrier, suggesting that soy lecithin may affect barrier integrity through mechanisms separate from its oxidative stress-related inflammatory effects.

DATEM also activated inflammatory and cell-death pathways but did not produce the same oxidative stress response. Overall, the researchers found that although soy lecithin and DATEM appeared to act through partly different biological mechanisms, both ultimately promoted inflammatory responses in intestinal cells. When cells were exposed to the emulsifiers together, several genes associated with inflammation, cellular stress, and epithelial function showed greater responses than with either emulsifier alone.

In mice given the emulsifiers once weekly for six weeks, the researchers observed inflammatory molecular changes throughout the gastrointestinal tract, including the esophagus, stomach, ileum, and colon. Changes became more pronounced toward the colon. Serum analyses also showed increases in multiple inflammatory and immune-related mediators, providing evidence that the effects were not limited to intestinal tissue.

Findings Point to Possible Role in Allergic Sensitization

The researchers also observed immune effects relevant to allergy development. Soy lecithin increased total IgE in mice. IgE is an antibody central to allergic reactions and sensitization. In experiments using immune cells from four healthy human donors, DATEM dose-dependently enhanced IgE production stimulated by the immune signaling molecule IL-4. Both emulsifiers also affected IgG, another class of antibodies involved in immune responses. The researchers suggested that these antibody responses could indicate that the emulsifiers influence immune activation.

Taken together, the barrier and immune findings provide a possible biological connection between emulsifier exposure and pathways involved in allergic sensitization. Damage to the intestinal barrier could increase contact between the immune system and substances in the gut, while changes in IgE-related responses could favor allergic sensitization.

However, the study did not demonstrate that consuming soy lecithin or DATEM causes food allergies or chronic disease in humans. Among the study's limitations, the researchers did not determine the exact concentrations of the emulsifiers that would reach the human gut, and the study did not include a chronic in vivo exposure model. The researchers also said that future studies should examine genetic susceptibility and the effects of the emulsifiers on the gut microbiota.

Researchers Call for Broader Food Additive Safety Assessments

The findings have implications for how food additive safety is evaluated, according to Cezmi Akdis, M.D., Professor at the University of Zurich and Director of the Swiss Institute of Allergy and Asthma Research (SIAF), who was the study's corresponding author.

Traditional toxicological assessments remain valuable for evaluating endpoints such as general toxicity, organ-specific damage, genotoxicity, carcinogenicity where applicable, and systemic exposure safety margins, Dr. Akdis explained to Food Safety Magazine. However, he said such approaches may miss gut-specific biological effects, including weakened intestinal barriers, altered immune responses, increased potential for allergic sensitization, and effects mediated by the gut microbiome.

Dr. Akdis told Food Safety Magazine that the findings ultimately support “a more comprehensive framework” for evaluating food additive safety. Such an approach would consider exposure and formulation alongside effects on intestinal barrier integrity and permeability, inflammatory and immune responses, and the intestinal microenvironment, in addition to conventional toxicological endpoints.

The intestinal microenvironment includes factors such as the composition and activity of the gut microbiota, the protective mucus layer, bile acids, nutrients and metabolites, and interactions between intestinal cells and microorganisms, Dr. Akdis explained. Emulsifiers could potentially affect these systems by changing microbial access to intestinal surfaces, influencing the mucus barrier or microbial metabolism, or altering the balance of microbial populations.

The study authors called for updated food additive risk assessment frameworks that account for gut permeability, immune activation, and microbiome alterations. They said future research should investigate long-term health outcomes and microbiome-emulsifier interactions, as well as identify safer food formulation strategies.