TY - JOUR T1 - RNA-Seq Profiling of Intestinal Expression of Xenobiotic Processing Genes in Germ-Free Mice JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.117.077313 SP - dmd.117.077313 AU - Zidong Donna Fu AU - Felcy P Selwyn AU - Julia Yue Cui AU - Curtis D. Klaassen Y1 - 2017/01/01 UR - http://dmd.aspetjournals.org/content/early/2017/09/22/dmd.117.077313.abstract N2 - Intestinal bacteria can affect xenobiotic metabolism through both direct bacterial enzyme-catalyzed modification of the xenobiotics and indirect alterations of the expression of host genes. In order to determine the effect of the lack of intestinal bacteria on the expression of xenobiotic-processing genes (XPGs) of the host intestine, the mRNA profiles of 303 XPGs were characterized by high-throughput RNA-sequencing in four sections of the intestine and compared to that in the liver from adult male conventional (CV) and germ-free (GF) mice. Among these, 54 XPGs were not expressed in the intestine of either CV or GF mice. GF condition altered the expression of 116 XPGs in at least one section of intestine, but had no effect on the intestinal expression of 133 XPGs. Many cytochrome P450s such as Cyp1a, Cyp2b10, Cyp2c, and most Cyp3a members, as well as carboxylesterase 2a were expressed lower in the intestine of GF than CV mice. In contrast, GF mice had higher intestinal expression of some phase-I oxidases (alcohol dehydrogenase 1, aldehyde dehydrogenase 1l1 and 4a1, as well as flavin monooxygenase 5) and phase-II conjugation enzymes (UDP-glucuronosyltransferase 1a1 and sulfotransferase 1c2, 1d1, and 2b1). Several transporters in the intestine exhibited higher expression in GF mice, such as the bile acid transporters (apical sodium-dependent bile acid transporter, organic solute transporter α and β), peptide transporter 1, and multidrug and toxin extrusion protein 1. In conclusion, lack of intestinal bacteria alters the expression of a large number of XPGs in the host intestine, and some of the alterations are section-specific. Cyp3a is down-regulated in both liver and intestine of GF mice, which probably is the most important determinant for altered xenobiotic metabolism due to the lack of intestinal bacteria. ER -