title: Starring role of toll-like receptor-4 activation in the gut-liver axis.
abstract: Since the introduction of the term "gut-liver axis", many studies have focused on the functional links of intestinal microbiota, barrier function and immune responses to liver physiology. Intestinal and extra-intestinal diseases alter microbiota composition and lead to dysbiosis, which aggravates impaired intestinal barrier function via increased lipopolysaccharide translocation. The subsequent increased passage of gut-derived product from the intestinal lumen to the organ wall and bloodstream affects gut motility and liver biology. The activation of the toll-like receptor 4 (TLR-4) likely plays a key role in both cases. This review analyzed the most recent literature on the gut-liver axis, with a particular focus on the role of TLR-4 activation. Findings that linked liver disease with dysbiosis are evaluated, and links between dysbiosis and alterations of intestinal permeability and motility are discussed. We also examine the mechanisms of translocated gut bacteria and/or the bacterial product activation of liver inflammation and fibrogenesis via activity on different hepatic cell types.
authors.affiliation: Simone Carotti, Sergio Morini, Laboratory of Microscopic and Ultrastructural Anatomy, School of Medicine, University Campus Bio-Medico of Rome, 00128 Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Carotti
authors.affiliation: Simone Carotti, Sergio Morini, Laboratory of Microscopic and Ultrastructural Anatomy, School of Medicine, University Campus Bio-Medico of Rome, 00128 Rome, Italy.
authors.forename: Michele Pier Luca
authors.initials: MP
authors.lastname: Guarino
authors.affiliation: Simone Carotti, Sergio Morini, Laboratory of Microscopic and Ultrastructural Anatomy, School of Medicine, University Campus Bio-Medico of Rome, 00128 Rome, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Vespasiani-Gentilucci
authors.affiliation: Simone Carotti, Sergio Morini, Laboratory of Microscopic and Ultrastructural Anatomy, School of Medicine, University Campus Bio-Medico of Rome, 00128 Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Morini
keywords: Chronic hepatitis; Dysbiosis; Gut microbiota; Gut motility; Intestinal barrier function; Lipopolysaccharide tolerance; Liver fibrosis; Non-alcoholic fatty liver disease; Toll-like receptor 4