Gut dysbiosis-derived low-grade endotoxemia: A common basis for liver and cardiovascular disease.

Abstract

Gut dysbiosis is characterized by bacteria overgrowth that ultimately leads to increased intestinal barrier permeability and translocation of bacteria or bacterial products such as lipopolysaccharide (LPS) in the portal and, eventually, systemic circulation. Intestinal epithelial cells and hepatocytes possess enzymatic armamentarium to counteract the LPS toxic effect, however, impaired degradation results in LPS accumulation in the hepatocytes and endothelial wall. Experimental and clinical studies documented that in patients with liver disease, such as nonalcoholic fatty acid liver disease (NAFLD), low-grade endotoxemia caused by LPS is implicated in liver inflammation and thrombosis via interaction with its Toll-like receptor 4 (TLR4) expressed by hepatocytes and platelets. Furthermore, studies in patients with severe atherosclerosis documented that LPS localizes in atherosclerotic plaque in close association with activated macrophages expressing TLR4 suggesting LPS's role in vascular inflammation, atherosclerotic progression, and thrombosis. Finally, LPS may directly interact with myocardial cells to induce electric and functional changes leading to atrial fibrillation or heart failure. This review will focus on experimental and clinical evidence suggesting that low-grade endotoxemia, as a mechanism, potentially accounts for vascular damage occurring at the level of the hepatic and systemic circulation and myocardial cells.