Dietary Carrageenan Amplifies the Inflammatory Profile, but not Permeability, of Intestinal Epithelial Cells from Patients With Crohn's Disease

Inflamm Bowel Dis. 2025 May 12;31(5):1392-1403. doi: 10.1093/ibd/izae306.

Abstract

Background: The consumption of ultra-processed foods has increased significantly worldwide and is associated with the rise in inflammatory bowel diseases. However, any causative factors and their underlying mechanisms are yet to be identified. This study aimed to further elucidate whether different types of the dietary emulsifier carrageenan (CGN) can alter the permeability and inflammatory state of the intestinal epithelium.

Methods: Caco-2/HT29-MTX cocultures (n = 4) were exposed to either κ-, ι-, or λ-CGN (100 µg mL-1) for 24 hours. Organoid-derived monolayers from patients with Crohn's Disease (CD) were exposed to κ-CGN (100 µg mL-1) for 48 hours (n = 10). In both models, an inflamed condition was established by adding a mix of inflammatory stimuli. Changes in permeability were measured by transepithelial electrical resistance (TEER). In the organoid-derived monolayers, cytokines were quantified in the apical and basolateral supernatant and gene expression was analyzed with RT-qPCR.

Results: None of the CGN subtypes altered permeability of non-inflamed or inflamed Caco-2/HT29-MTX cocultures. In organoid-derived monolayers, κ-CGN did not affect TEER, but induced alterations in the gene expression of tight junctions and mucus proteins. Expression of TNF, IL8, and IL1B increased upon κ-CGN stimulation, both in inflamed and non-inflamed monolayers. Cytokine release in the supernatant was increased by κ-CGN for IL-6, IL-13, IL-4, IL-2, and IL-10.

Conclusions: Dietary CGN caused upregulation of inflammatory markers and affected cytokine release of intestinal epithelial cells from CD patients, while permeability remained unaltered. When inflammation was already present, this pro-inflammatory effect was more pronounced, suggesting a role for dietary CGN during active CD.

Keywords: emulsifiers; inflammatory bowel diseases; intestinal epithelium; organoids; ultra-processed foods.

Plain language summary

This study revealed that the dietary emulsifier carrageenan has direct pro-inflammatory effects on intestinal epithelial cells from patients with Crohn’s disease, without affecting permeability. In an inflamed setting, this was more pronounced, suggesting a role for dietary carrageenan during active inflammation.

MeSH terms

  • Adult
  • Caco-2 Cells
  • Carrageenan* / adverse effects
  • Carrageenan* / pharmacology
  • Coculture Techniques
  • Crohn Disease* / metabolism
  • Crohn Disease* / pathology
  • Cytokines / metabolism
  • Epithelial Cells* / drug effects
  • Epithelial Cells* / metabolism
  • Epithelial Cells* / pathology
  • Female
  • HT29 Cells
  • Humans
  • Inflammation* / chemically induced
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Intestinal Mucosa* / drug effects
  • Intestinal Mucosa* / metabolism
  • Intestinal Mucosa* / pathology
  • Male
  • Permeability / drug effects

Substances

  • Carrageenan
  • Cytokines