These authors contributed equally to this study.
Nondigestible oligosaccharides exert nonprebiotic effects on intestinal epithelial cells enhancing the immune response via activation of TLR4-NFκB
Article first published online: 3 SEP 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 2, pages 384–393, February 2014
How to Cite
Ortega-González, M., Ocón, B., Romero-Calvo, I., Anzola, A., Guadix, E., Zarzuelo, A., Suárez, M. D., Sánchez de Medina, F. and Martínez-Augustin, O. (2014), Nondigestible oligosaccharides exert nonprebiotic effects on intestinal epithelial cells enhancing the immune response via activation of TLR4-NFκB. Mol. Nutr. Food Res., 58: 384–393. doi: 10.1002/mnfr.201300296
- Issue published online: 3 FEB 2014
- Article first published online: 3 SEP 2013
- Manuscript Accepted: 2 JUL 2013
- Manuscript Revised: 19 JUN 2013
- Manuscript Received: 23 APR 2013
- Ministerio de Ciencia e Innovación. Grant Numbers: SAF2008–01432, AGL2008–04332, SAF2011–22922, SAF2011–22812
- Junta de Andalucía. Grant Numbers: CTS-6736, CTS164
- Fundación Ramón Areces
- Ministerio de Educación
- Instituto de Salud Carlos III
- Intestinal epithelial cells;
- Toll-like receptor 4
Prebiotic effects of non absorbable glucids depend mainly on digestion by the colonic microbiota. Our aim was to assess nonprebiotic, direct effects of 4 prebiotics, namely fructooligosaccharides, inulin, galactooligosaccharides, and goat's milk oligosaccharides on intestinal epithelial cells.
Methods and results
Prebiotics were tested in intestinal epithelial cell 18 (IEC18), HT29, and Caco-2 cells. Cytokine secretion was measured by ELISA and modulated with pharmacological probes and gene silencing. Prebiotics induced the production of growth-related oncogene, (GROα), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 2 (MIP2) in IEC18 cells, with an efficacy that was 50–80% that of LPS. Prebiotics did not change RANTES expression, which was robustly induced by LPS in IEC18 cells. Cytokine secretion was suppressed by Bay11-7082, an inhibitor of IκB-α phosphorylation. The response was markedly decreased by Myd88 or TLR4 gene knockdown. Prebiotics also elicited cytokine production in HT29 but not in Caco-2 cells, consistent with reduced and vestigial expression of TLR4 in these cell lines, respectively. Prebiotic-induced MCP-1 secretion was reduced also in colonic explants from TLR4 KO mice compared with the controls.
We conclude that prebiotics are TLR4 ligands in intestinal epithelial cells and that this may be a relevant mechanism for their in vivo effects.