Blueberries Reduce Palm Oil-Induced Metabolic Endotoxemia in an In Vitro Human Intestinal-Immune Cell Model

Metabolic endotoxemia (ME), a dietary lipid-induced increase in plasma LPS levels, is associated with cardiometabolic conditions. Accumulating evidence suggests an association between berry consumption and reduced endotoxemia. However, the underlying mechanisms remain unknown. This study examined the effects and potential mechanisms of blueberries, blackberries, and bananas on ME using an in vitro human intestinal-immune cell model. Palm oil with LPS was added to intestinal Caco-2 cells seeded on Transwell inserts, recapitulating dietary fat absorption. Higher levels of basolateral LPS were observed when Caco-2 cells were cotreated with palm oil and LPS compared to control and LPS, supporting lipid-induced LPS translocation. To examine the bioactivity of translocated LPS, THP1-Lucia nuclear factor kappa B (NF-κB) macrophages were exposed to basolateral conditioned media from Caco-2 cells, and NF-κB activation was assessed. Basolateral conditioned medium from Caco-2 cells cotreated with digested palm oil and LPS induced higher macrophage NF-κB activation compared to only palm oil. Interestingly, fruits reduced the palm oil + LPS-mediated NF-κB activation in macrophages. Transcriptomic and protein-level analyses suggest berries modulate the lipid-induced LPS translocation, likely via clathrin-mediated transcytosis with a minor chylomicron-mediated contribution. The anti-inflammatory effects of berry-rich diets may be mediated by preventing ME.