Common Food Emulsifiers Impair Epithelial Barrier Integrity and Trigger Pro‐Inflammatory Responses and IgE Production

ABSTRACT

The global rise in allergic and autoimmune diseases since the 1960s has been associated with environmental disruptions of epithelial barriers, particularly in the gastrointestinal tract. Among the implicated factors are food emulsifiers, which have become increasingly prevalent in processed foods such as peanut butter. This study investigates the biological effects of two commonly used food emulsifiers in peanut butter, soy lecithin and diacetyl tartaric acid esters of mono‐ and diglycerides (DATEM), on gastrointestinal tissue responses and immune responses using advanced in vitro gut‐on‐a‐chip models, human adult stem cell‐derived colon organoids‐on‐a‐chip, and murine models. Both emulsifiers induced dose‐dependent cytotoxicity and disrupted epithelial barriers, as demonstrated by reduced transepithelial electrical resistance and disorganization of zona occludens‐1 at daily‐exposure doses. Transcriptomic and proteomic analyses revealed activation of pro‐inflammatory pathways including TNF, NF‐κB, the unfolded protein response, and cell death by apoptosis. Soy lecithin additionally induced oxidative stress. Systemic responses were confirmed by increased pro‐inflammatory cytokines in serum and immune activation in peripheral blood mononuclear cells (PBMCs). Notably, both emulsifiers stimulated serum total IgG, soy lecithin induced IgE in mice upon feeding, and DATEM enhanced IL‐4‐induced IgE production in human PBMCs, suggesting a role in allergy development. These findings challenge the presumed safety of soy lecithin and DATEM and highlight their potential contribution to immune dysregulation and epithelial barrier dysfunction, which may initiate or exacerbate food allergy and gastrointestinal inflammatory diseases.