SINTESI CONTENENTE UNA BREVE DESCRIZIONE DEL LAVORO SVOLTO E DEI RISULTATI OTTENUTI: In healthy individuals, the intestinal microbiota cannot access the liver, spleen or other peripheral tissues. Some pathogenic bacteria can reach these sites, however, inducing a systemic immune response. How such discrimination is achieved is unknown. We identify a gut-vascular barrier (GVB) in mice and humans that controls the translocation of antigens into the blood stream and prohibits entry of the microbiota. Salmonella typhimurium can penetrate the GVB in manner dependent on its pathogenicity island (spi)-2-encoded type-three secretion system and on decreased β-catenin-dependent signaling in gut endothelial cells. We found that GVB is modified also in celiac disease patients with elevated serum t ransaminases, indicating that GVB dismantling may be responsible for liver damage in these patients. Understanding the GVB may provide new insights into the regulation of the gut-liver axis.