Mechanisms of gut epithelial barrier impairment caused by food emulsifiers polysorbate 20 and polysorbate 80

Abstract

BackgroundThe rising prevalence of many chronic diseases related to gut barrier dysfunction coincides with the increased global usage of dietary emulsifiers in recent decades. We therefore investigated the effect of the frequently used food emulsifiers on cytotoxicity, barrier function, transcriptome alterations, and protein expression in gastrointestinal epithelial cells.MethodsHuman intestinal organoids originating from induced pluripotent stem cells, colon organoid organ‐on‐a‐chip, and liquid–liquid interface cells were cultured in the presence of two common emulsifiers: polysorbate 20 (P20) and polysorbate 80 (P80). The cytotoxicity, transepithelial electrical resistance (TEER), and paracellular‐flux were measured. Immunofluorescence staining of epithelial tight‐junctions (TJ), RNA‐seq transcriptome, and targeted proteomics were performed.ResultsCells showed lysis in response to P20 and P80 exposure starting at a 0.1% (v/v) concentration across all models. Epithelial barrier disruption correlated with decreased TEER, increased paracellular‐flux and irregular TJ immunostaining. RNA‐seq and targeted proteomics analyses demonstrated upregulation of cell development, signaling, proliferation, apoptosis, inflammatory response, and response to stress at 0.05%, a concentration lower than direct cell toxicity. A proinflammatory response was characterized by the secretion of several cytokines and chemokines, interaction with their receptors, and PI3K‐Akt and MAPK signaling pathways. CXCL5, CXCL10, and VEGFA were upregulated in response to P20 and CXCL1, CXCL8 (IL‐8), CXCL10, LIF in response to P80.ConclusionsThe present study provides direct evidence on the detrimental effects of food emulsifiers P20 and P80 on intestinal epithelial integrity. The underlying mechanism of epithelial barrier disruption was cell death at concentrations between 1% and 0.1%. Even at concentrations lower than 0.1%, these polysorbates induced a proinflammatory response suggesting a detrimental effect on gastrointestinal health.

Recent advances in the epithelial barrier theory

“…The two frequently used food emulsifiers, polysorbates 20 and 80, were recently reported for their cellular toxicity, damage to epithelial barriers, transcriptome alterations, and protein expression in gastrointestinal epithelial cells. Although 1% is allowed, epithelial barrier disruption, upregulation of apoptosis, inflammatory responses, and stress responses were observed at 20 times lower (0.05%) concentrations ( 71 ). Moreover, the consumption of processed foods has been linked to various health issues, including all-cause mortality, obesity, metabolic syndrome, and depression ( 72 ).…”

Skin, gut, and lung barrier: Physiological interface and target of intervention for preventing and treating allergic diseases

“…Ultra‐processed foods contain high levels of dietary advanced glycation end products, which may facilitate food allergy by impairing the gut barrier and by inducing immune dysfunction 107 . Furthermore, food emulsifiers induce a pro‐inflammatory response in intestinal epithelial barriers and cause direct cell toxicity at high concentrations 108 . Food colourants have been shown to cause epithelial damage in mice via myosin light chain kinase activation 109 …”

Epithelial Barrier Theory: The Role of Exposome, Microbiome, and Barrier Function in Allergic Diseases

“…Studies suggest that these products may enhance bacterial translocation across mucosal surfaces, affect the gut epithelial mucous layer, alter microbial composition, and contribute to the development of intestinal inflammation. 126 127 128 129 Recent study has shown that commonly used food emulsifiers, polysorbate 20 and polysorbate 80, cause cell death at daily-used concentrations, directly impair barrier integrity of gut epithelial cells, and cause molecular toxicity and proinflammation at lower doses. 129 …”

“… 126 127 128 129 Recent study has shown that commonly used food emulsifiers, polysorbate 20 and polysorbate 80, cause cell death at daily-used concentrations, directly impair barrier integrity of gut epithelial cells, and cause molecular toxicity and proinflammation at lower doses. 129 …”