Immunomodulatory activity of a gut microbial metabolite of dietary linoleic acid, 10-hydroxy-cis-12-octadecenoic acid, associated with improved antioxidant/detoxifying defences

Various hydroxy-, oxo-, and conjugated fatty acids are generated by gut microbes throughout the metabolism of dietary PUFAs. Specifically, 10-Hydroxy-cis-12-(HYA), 10-oxo-cis12-(KetoA) and 10-oxo-cis9,trans11-octadecenoic acid (KetoC) are intermediates free fatty acids (iFFA) produced during the isomerization of dietary linoleic acid to cis9,trans11 (c9,t11) isomer of conjugated linoleic acid (CLA). Herein, immunomodulatory and antioxidant activity of selected iFFA was studied in resting (iDCs), LPS-matured DCs (mDCs) and inmurine enterocyte cells (MODE-K). Phenotypic maturation of iDCs was not influenced by iFFA, but the release of pro-inflammatory molecules from mDCs was reduced following HYA pre-treatment. HYA ability to improve antioxidant/detoxifying defenses associated with decreased expression of maturation markers in mDCs and in MODE-K cells. The pro-oxidant activity, via NADPH oxidase activation, was responsible for the pro-inflammatory effect of 10-hydroxyoctadecanoic acid. Presented data suggest that the immunomodulatory ability of HYA is determined, at least in part, by its ability to improve antioxidant/detoxifying defenses.