Gastro-intestinal and hepatic mechanisms limiting the entry and dissemination of lipopolysaccharide into the systemic circulation

International audienceThe human microbiota consists of 100 trillion microorganisms that provide important metabolic and biological functions benefiting the host. However, the presence in host plasma of a gut derived-bacteria component, the lipopolysaccharide (LPS), has been identified as a causal or complicating factor in multiple serious diseases like sepsis and septic shock and more recently obesity-associated metabolic disorders. Understanding the precise mechanisms by which gut-derived LPS is transported from the gut lumen to the systemic circulation is crucial to advance our knowledge in LPS-associated diseases and elaborate targeted strategies for their prevention. The aim of this review is to synthetize the current knowledge on the host mechanisms limiting the entry and dissemination of LPS into the systemic circulation. To prevent bacterial colonization and penetration, the intestinal epithelium harbors multiple defense mechanisms including the secretion of anti-microbial peptides and mucins as well as detoxification enzymes. Despite this first line of defense, LPS can reach the apical site of intestinal epithelial cells (IEC) and, due to its large size, likely crosses IEC via a transcellular transport, either lipid raft or clathrin-mediated endocytosis or goblet-cell associated passage. However, the precise pathway remains poorly described. Finally, if LPS crosses the gut mucosa, it is directed to the liver via the portal vein where major detoxification processes occur by deacetylation and excretion through the bile. If this disposal process is not sufficient, LPS enters the systemic circulation where it is handled by numerous transport proteins that clear it back to the liver for further excretion