title: Gastrointestinal and hepatic mechanisms limiting entry and dissemination of lipopolysaccharide into the systemic circulation.
abstract: The 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 such as 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 of LPS-associated diseases and elaborate targeted strategies for their prevention. The aim of this review is to synthetize 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 antimicrobial peptides and mucins as well as detoxification enzymes. Despite this first line of defense, LPS can reach the apical site of intestinal epithelial cells (IECs) and, because of its large size, likely crosses IECs via 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 via the portal vein to the liver, 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.
authors.affiliation: INRA UR1341 ADNC, Domaine de la Prise, Saint-Gilles, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Guerville
authors.affiliation: INRA UR1341 ADNC, Domaine de la Prise, Saint-Gilles, France gaelle.boudry@rennes.inra.fr.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Boudry
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology / Q000378:metabolism*; D018988:Bacterial Translocation; D000069196:Gastrointestinal Microbiome; D054884:Host-Pathogen Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008070:Lipopolysaccharides / Q000097:blood* / Q000737:chemistry; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D010539:Permeability; D018805:Sepsis / Q000097:blood* / Q000276:immunology / Q000382:microbiology
chemical_list: D008070:Lipopolysaccharides
keywords: antimicrobial peptides; intestinal barrier function; liver LPS detoxification; metabolic endotoxemia; sepsis