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The presence of bacterial endotoxin in the bloodstream, known as endotoxemia, may cause inflammation and play a role in the development of chronic disease. Dietary fatty acid composition has been demonstrated, albeit inconsistently in different animal species, to modulate endotoxemia potentially via altered lipopolysaccharide (LPS) absorption from the intestinal lumen. We first sought to uncover whether postprandial endotoxemia in healthy people is influenced by the consumption of meals rich in saturated or long-chain n(ω)-3 fatty acids, respectively. Considering the physiological similarity of the human and porcine gastrointestinal tracts, the effect on endotoxemia from long-term consumption of high fat diets distinct in fatty acid composition was examined in pigs. Mechanistic investigations were performed in porcine tissue in vitro and ex vivo to understand how dietary fatty acids might differently regulate LPS transport and LPS-induced inflammation at the intestinal epithelium. Previous studies using human participants have indicated that the consumption of a high-fat meal is associated with increased postprandial endotoxemia and circulating markers of inflammation. However, it was unclear whether this effect was dependent on high or low fat content or the fatty acid composition of the meal. To address this question, healthy adult men and women were recruited for a randomized cross-over study in which participants consumed a low-fat meal, or one of three high-fat meals containing saturated, n-3, or n-6 fatty acids. Serum endotoxin concentration was lower (p<0.05) following the consumption of an n-3 fatty-acid rich meal compared to serum endotoxin concentration after the consumption of a saturated fatty acid-rich meal. Postprandial endotoxemia was not different regardless if the participant had consumed a low-fat content or high fat content meal. Despite alterations in blood endotoxin,

A translational investigation into the role of dietary fatty acids in modulating endotoxemia and associated inflammation