(B) relative levels of Fgf15 transcripts in the ilea of infected mice (data by qPCR). (C) H&E staining of ileum sections from representative uninfected and orally Salmonella-infected animals (ileal colonization of the infected animal = 2.2 × 106 cfu/mg); scale bars are 200 μm. (D) H&E staining of liver sections from representative uninfected and orally Salmonella-infected

animals (liver colonization of the infected animal = 1.7 × 105 cfu/mg); scale bars are 800 and 400 μm. FGF15 is synthesized by enterocytes [6], which can also be invaded by Salmonella[23]. However, the decrease in Fgf15 expression was not associated with damage to the ileal enterocyte layer (Figure 1C). This suggests that loss of ileal enterocytes is not the reason for reduced Lazertinib cell line Fgf15 transcript levels. Oral infections with Listeria monocytogenes, an inefficient invader of the mouse buy Osimertinib intestinal epithelium [24, 25], showed no significant liver colonization and large numbers of intestinal bacteria but not downregulation

of Fgf15 expression (Figure 2A). In contrast, intravenous infections with Listeria, which colonized the Selleckchem GS-9973 liver rapidly and triggered deccreases in the transcript levels of biliary function genes (Figure 2B), caused a significant reduction in ileal Fgf15 expression (Figure 2A). These results point to hepatic pathophysiology, rather than intestinal bacterial colonization, as the primary event driving downregulation of intestinal Fgf15 expression. Figure 2 Liver colonization drives the downregulation of ileal Fgf15 expression. (A) relative levels of Fgf15 transcripts in the ileum of mice infected orally or intravenously with Listeria monocytogenes. (B) transcript levels of genes involved in liver biliary metabolism in mice infected intravenously with Listeria monocytogenes, relative to the levels of uninfected animals (defined as 1, dashed line). (C) relative levels of Fgf15 transcripts in (-)-p-Bromotetramisole Oxalate the ilea of mice infected intravenously with Salmonella typhimurium SB103 (invA), at 120 hours post-infection. Data by qPCR, *p < 0.05. To establish the role of hepatic colonization and to probe the involvement of bacterial enterocyte invasion in repressing

Fgf15 expression, we carried out intravenous infections with the Salmonella invasion-deficient strain SB103 following Menendez et al.[22]. In this type of infection, Salmonella colonization of the hepatobiliary system occurs immediately whereas colonization of the gut is delayed by 72 to 96 hours [22]. Furthermore, the bacteria that eventually reach the intestines are unable to invade the enterocytes due to the invA mutation of this strain. As shown in Figure 2C, intravenous infection with Salmonella SB103 caused a reduction of Fgf15 transcripts abundance. Notably, such a decrease was observed with a much lower intestinal bacterial burden than those in oral infections with the wild-type strain (average 102 vs. 107 cfu/mg, respectively).