The probiotic, Lactobacillus casei , prevents cholesteryl‐ester (CE) accumulation and LPS antagonism of LXR‐responsive genes in alveolar macrophages from Ossabaw pigs fed a high fat/high cholesterol (HF/HC) diet

High fat diets can lead to dyslipidemia and promote pro‐inflammatory mediators, but modulators of inflammation may reduce diet‐induced pathologies. We tested the hypothesis that daily feeding of L. casei to juvenile Ossabaw pigs fed a HF/HC diet would modulate cholesterol metabolism and innate immune responses of isolated alveolar macrophages (AM). We observed that AM from pigs fed a HF/HC diet had significantly higher concentrations of CE than AM from pigs fed a control diet (CD). Feeding L. casei significantly attenuated this effect. AM from pigs fed a HF/HC diet exhibited increased LPS‐induced expression of mRNA and protein for IL1B and IL8 that was not affected by feeding L. casei ; although AM from CD fed pigs given L. casei had significantly higher LPS‐induced mRNA levels of IL1B, IL8, and IL6. Ex‐vivo treatment with a specific LXR ligand opposed the inflammatory effects of LPS in AM from pigs fed a HF/HC diet or HF/HC diet and L. casei , but not in AM from pigs fed the CD. Lastly, we observed that LPS significantly inhibited cholesterol metabolism related genes LXRα, ABCA1, ABCG1, and CH25H in AM from pigs fed either HF/HC diet or CD. This effect was ablated in AM from pigs fed HF/HC diet and L. casei . Feeding L. casei prevented CE accumulation in AM from pigs fed a HF/HC diet and opposed the LPS antagonism of the LXR and cholesterol metabolism related genes indicating a role in modulating lung inflammation.