AUTHOR=Lamas-Paz Arantza , Morán Laura , Peng Jin , Salinas Beatriz , López-Alcántara Nuria , Sydor Svenja , Vilchez-Vargas Ramiro , Asensio Iris , Hao Fengjie , Zheng Kang , Martín-Adrados Beatriz , Moreno Laura , Cogolludo Angel , Gómez del Moral Manuel , Bechmann Lars , Martínez-Naves Eduardo , Vaquero Javier , Bañares Rafael , Nevzorova Yulia A. , Cubero Francisco Javier TITLE=Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury JOURNAL=Frontiers in Pharmacology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.603771 DOI=10.3389/fphar.2020.603771 ISSN=1663-9812 ABSTRACT=
Binge drinking, i.e., heavy episodic drinking in a short time, has recently become an alarming societal problem with negative health impact. However, the harmful effects of acute alcohol injury in the gut-liver axis remain elusive. Hence, we focused on the physiological and pathological changes and the underlying mechanisms of experimental binge drinking in the context of the gut-liver axis. Eight-week-old mice with a C57BL/6 background received a single dose (p.o.) of ethanol (EtOH) [6 g/kg b.w.] as a preclinical model of acute alcohol injury. Controls received a single dose of PBS. Mice were sacrificed 8 h later. In parallel, HepaRGs and Caco-2 cells, human cell lines of differentiated hepatocytes and intestinal epithelial cells intestinal epithelial cells (IECs), respectively, were challenged in the presence or absence of EtOH [0–100 mM]. Extracellular vesicles (EVs) isolated by ultracentrifugation from culture media of IECs were added to hepatocyte cell cultures. Increased intestinal permeability, loss of zonula occludens-1 (ZO-1) and MUCIN-2 expression, and alterations in microbiota—increased