Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids
Journal article, 2022

Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography–mass spectrometry and distinguished patients with CC (n = 6), UC (n = 6), IBS (n = 6) and healthy subjects (n = 6). Caco-2 monolayers and human apical-out colonoids underwent stimulation with fecal supernatants from different patient groups and healthy subjects. Their addition did not impair monolayer integrity, as measured by transepithelial electrical resistance; however, fecal supernatants from different patient groups and healthy subjects altered the gene expression of Caco-2 monolayers, as well as colonoid cultures. In conclusion, the stimulation of Caco-2 cells and colonoids with fecal supernatants derived from CC, UC and IBS patients altered gene expression profiles, potentially reflecting the luminal microenvironment of the fecal sample donor. This experimental approach allows for investigating the crosstalk at the gut barrier and the effects of the gut microenvironment in the pathogenesis of intestinal diseases.

irritable bowel syndrome


gut barrier

ulcerative colitis

host–microbial crosstalk

colon cancer


fecal metabolites


Luiza Moraes Holst

University of Gothenburg

Cristina Iribarren

University of Gothenburg

Maria Sapnara

University of Gothenburg

Otto Savolainen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

University of Eastern Finland

H. Törnblom

University of Gothenburg

Yvonne Wettergren

Sahlgrenska University Hospital

Hans Strid

Södra Älvsborg Hospital (SÄS)

M. Simren

University of Gothenburg

Maria K. Magnusson

University of Gothenburg

Lena Öhman

University of Gothenburg

International Journal of Molecular Sciences

16616596 (ISSN) 14220067 (eISSN)

Vol. 23 24 15505

Subject Categories

Clinical Laboratory Medicine

Gastroenterology and Hepatology






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1/9/2023 1