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Nondigestible oligosaccharides exert nonprebiotic effects on intestinal epithelial cells enhancing the immune response via activation of TLR 4‐ NF κ B
Author(s) -
OrtegaGonzález Mercedes,
Ocón Borja,
RomeroCalvo Isabel,
Anzola Andrea,
Guadix Emilia,
Zarzuelo Antonio,
Suárez Maria D.,
Sánchez de Medina Fermin,
MartínezAugustin Olga
Publication year - 2014
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300296
Subject(s) - prebiotic , cytokine , secretion , immune system , monocyte , chemistry , caco 2 , iκbα , nf κb , biology , cell , signal transduction , immunology , biochemistry
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 ( IEC 18), HT 29, 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 IEC 18 cells, with an efficacy that was 50–80% that of LPS . Prebiotics did not change RANTES expression, which was robustly induced by LPS in IEC 18 cells. Cytokine secretion was suppressed by B ay11‐7082, an inhibitor of I κ B ‐α phosphorylation. The response was markedly decreased by M yd88 or TLR 4 gene knockdown. Prebiotics also elicited cytokine production in HT 29 but not in C aco‐2 cells, consistent with reduced and vestigial expression of TLR 4 in these cell lines, respectively. Prebiotic‐induced MCP‐1 secretion was reduced also in colonic explants from TLR 4 KO mice compared with the controls. Conclusions We conclude that prebiotics are TLR 4 ligands in intestinal epithelial cells and that this may be a relevant mechanism for their in vivo effects.