Nondigestible oligosaccharides exert nonprebiotic effects on intestinal epithelial cells enhancing the immune response via activation of TLR4-NFκB

Authors

  • Mercedes Ortega-González,

    1. Department of Biochemistry and Molecular Biology II, CIBERehd, School of Pharmacy, University of Granada, Granada, Spain
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    • These authors contributed equally to this study.

  • Borja Ocón,

    1. Department of Pharmacology, CIBERehd, School of Pharmacy, University of Granada, Granada, Spain
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    • These authors contributed equally to this study.

  • Isabel Romero-Calvo,

    1. Department of Biochemistry and Molecular Biology II, CIBERehd, School of Pharmacy, University of Granada, Granada, Spain
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  • Andrea Anzola,

    1. Department of Pharmacology, CIBERehd, School of Pharmacy, University of Granada, Granada, Spain
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  • Emilia Guadix,

    1. Department of Chemical Engineering, University of Granada, Granada, Spain
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  • Antonio Zarzuelo,

    1. Department of Pharmacology, CIBERehd, School of Pharmacy, University of Granada, Granada, Spain
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  • Maria D. Suárez,

    1. Department of Biochemistry and Molecular Biology II, CIBERehd, School of Pharmacy, University of Granada, Granada, Spain
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  • Fermin Sánchez de Medina,

    1. Department of Pharmacology, CIBERehd, School of Pharmacy, University of Granada, Granada, Spain
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  • Olga Martínez-Augustin

    Corresponding author
    1. Department of Biochemistry and Molecular Biology II, CIBERehd, School of Pharmacy, University of Granada, Granada, Spain
    • Correspondence: Dr. Olga Martínez-Augustin, Biochemistry and Molecular Biology II, CIBERehd, School of Pharmacy, University of Granada, Granada, Spain

      E-mail: omartine@ugr.es

      Fax: +34-958-248960

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Abstract

Scope

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.

Conclusions

We conclude that prebiotics are TLR4 ligands in intestinal epithelial cells and that this may be a relevant mechanism for their in vivo effects.

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