Transcriptomic analysis of epithelitis caused by Aspartame

Pat Y., Yazıcı D., Garcıa-Sanchez A., Ardıçlı S., Sımmons S., Almada A., ...More

World Immune Regulation Meeting XVIII 2024, Chur, Switzerland, 13 - 16 March 2024, vol.18, no.48, pp.64-65

  • Publication Type: Conference Paper / Summary Text
  • Volume: 18
  • City: Chur
  • Country: Switzerland
  • Page Numbers: pp.64-65
  • Bursa Uludag University Affiliated: Yes


The globalization of the Western diet and the modern food industry increases human exposure to food additives, such as sweeteners. Aspartame, a widely used sweetener, is found in tabletop sweeteners, chewing gums, food supplements, and artificially sweetened beverages in the range of 25-500,000 mg/kg or mg/L. Yet, little is known about the effect of aspartame on gastrointestinal epithelial cell physiology. We investigated its effect on the gut epithelial barrier and its inflammatory effect using a gut-on-a-chip model, transcriptomic, and targeted proteomics. We found that exposure to 10 mg/ ml (10000 mg/kg or mg/L), a dose that is allowed and can be achieved in tabletop sweeteners, aspartame causes gut epithelial barrier impairment. RNA sequencing transcriptomic analysis demonstrated this exposure leads to upregulation of genes related to cellular stress, unfolded protein response, response to chemicals, programmed cell death and response to oxygen-containing compound pathways. In contrast, the transcription process and protein synthesis were downregulated. Aspartame upregulated endoplasmic reticulum stress-related genes (PMAIP1, BBC3, MCL1, ATF6, XBP1, ATF4, ATF3, DDIT3) through the unfolded protein response and induced upregulation of programmed cell death pathway. In addition, genes related to TNF and MAPK pathways are also upregulated. The end products of the TNF signalling pathway, such as CXCL1, CXCL2, CXCL3, CCL20, and PTGS2 genes, are upregulated. Proteomics by proximity extension assay aligns with transcriptomic data, revealing increased protein levels of TNF, CXCL1, and CCL20 in the culture supernatants. Overall, exposure to 10 mg/ml (10000 mg/kg or mg/L) aspartame leads to epithelitis on gut epithelial cells characterized by epithelial barrier impairment and inflammatory response.