The role of gut-derived oxidized lipids and bacterial lipopolysaccharide in systemic inflammation and atherosclerosis

Purpose of review This review explores mechanisms by which gut-derived bacterial lipopolysaccharide (LPS) and oxidized phospholipids contribute to chronic systemic inflammation and atherosclerosis. Recent findings Gut-derived LPS enters through the small intestine via two distinct pathways that involve high density lipoproteins (HDL) and chylomicrons. Gut-derived LPS can bind to the LPS-binding protein (LBP) and to HDL3 in the small intestine and travel through the portal vein to the liver where it does not elicit an inflammatory reaction, and is inactivated or it can bind to HDL2 and travel through the portal vein to the liver where it elicits an inflammatory reaction. Alternatively, in the small intestine, LPS can bind to LBP and chylomicrons and travel through the lymphatics to the systemic circulation and enhance inflammatory processes including atherosclerosis. Oxidized phospholipids formed in the small intestine regulate the levels and uptake of LPS in small intestine by regulating antimicrobial proteins such as intestinal alkaline phosphatase. Gut-derived LPS and oxidized phospholipids may be responsible for the persistent inflammation seen in some persons with human immunodeficiency virus on potent antiretroviral therapy with undetectable virus levels. By targeting gut-derived oxidized phospholipids, the uptake of gut-derived LPS may be reduced to decrease systemic inflammation and atherosclerosis.