The dietary emulsifier polysorbate-80 induces lipid accumulation and cell death in intestinal epithelial cells via ferroptosis

Chronic inflammatory and metabolic diseases are major global health issues increasingly linked to dietary factors. Consumption of dietary emulsifiers like polysorbate-80 (p80), common in ultra-processed foods and pharmaceuticals, has raised concerns about gut health. RNA sequencing on intestinal epithelial cells (IECs) exposed to p80 revealed increased expression of ferroptosis-associated genes and disruption of lipid metabolism pathways further demonstrated by mitochondrial dysfunction, including altered membrane potential and architecture, and accumulation of reactive oxygen species, iron, lipid peroxidation, and lipid droplet formation. Lipidomic profiling identified significant alterations in triglyceride species and elevated pro-ferroptotic polyunsaturated fatty acids. These data indicate that p80 disrupts lipid homeostasis in IECs and triggers ferroptotic cell death, mechanisms potentially contributing to the increased incidence of chronic conditions like inflammatory bowel disease and metabolic syndrome. The study highlights critical implications for public health, emphasizing the need for reassessment of emulsifier safety standards while balancing needs with consumer safety.