title: Gut-liver axis and sensing microbes.
abstract: 'Detoxification' of gut-derived toxins and microbial products from gut-derived microbes is a major role of the liver. While the full repertoire of gut-derived microbial products that reach the liver in health and disease is yet to be explored, the levels of bacterial lipopolysaccharide (LPS), a component of Gram-negative bacteria, is increased in the portal and/or systemic circulation in several types of chronic liver diseases. Increased gut permeability and LPS play a role in alcoholic liver disease where alcohol impairs the gut epithelial integrity through alterations in tight junction proteins. In addition, non-alcoholic fatty liver disease is also associated with increased serum LPS levels and activation of the pro-inflammatory cascade plays a central role in disease progression. Microbial danger signals are recognized by pattern recognition receptors such as the Toll-like receptor 4 (TLR4). Increasing evidence suggests that TLR4-mediated signaling via the MyD88-dependent or MyD88-independent pathways may play different roles in liver diseases associated with increased LPS exposure of the liver as a result of gut permeability. For example, we showed that in alcoholic liver disease, the MyD88-independent, IRF3-dependent TLR4 cascade plays a role in steatosis and inflammation. Our recent data demonstrate that chronic alcohol exposure in the liver leads to sensitization of Kupffer cells to LPS via a mechanism involving upregulation of microRNA-155 in Kupffer cells. Thus, understanding the cell-specific recognition and intracellular signaling events in sensing gut-derived microbes will help to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases.
authors.affiliation: University of Massachusetts Medical School, Worcester, Mass., USA. gyongyi.szabo@umassmed.edu
authors.forename: Gyongyi
authors.initials: G
authors.lastname: Szabo
authors.forename: Shashi
authors.initials: S
authors.lastname: Bala
authors.forename: Jan
authors.initials: J
authors.lastname: Petrasek
authors.forename: Arijeet
authors.initials: A
authors.lastname: Gattu
mesh_terms: D000818:Animals; D004194:Disease; D041981:Gastrointestinal Tract / Q000382:microbiology* / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000382:microbiology* / Q000502:physiology*; D054892:Metagenome / Q000502:physiology*; D010539:Permeability