title: Antibacterial drug treatment increases intestinal bile acid absorption via elevated levels of ileal apical sodium-dependent bile acid transporter but not organic solute transporter α protein.
abstract: Antibacterial drug treatment increases the bile acid pool size and hepatic bile acid concentration through the elevation of hepatic bile acid synthesis. However, the involvement of intestinal bile acid absorption in the increased bile acid pool size remains unclear. To determine whether intestinal bile acid absorption contributes to the increased bile acid pool in mice treated with antibacterial drugs, we evaluated the levels of bile acid transporter proteins and the capacity of intestinal bile acid absorption. Ileal apical sodium-dependent bile acid transporter (ASBT) mRNA and protein levels were significantly increased in ampicillin (ABPC)-treated mice, whereas organic solute transporter α (OSTα) mRNA levels, but not protein levels, significantly decreased in mice. Similar alterations in the expression levels of bile acid transporters were observed in mice treated with bacitracin/neomycin/streptomycin. The capacity for intestinal bile acid absorption was evaluated by an in situ loop method. Increased ileal absorption of taurochenodeoxycholic acid was observed in mice treated with ABPC. These results suggest that intestinal bile acid absorption is elevated in an ASBT-dependent manner in mice treated with antibacterial drugs.
authors.affiliation: Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578; Department of Food Science and Technology, National Fisheries University, 2-7-1 Nagatahonmachi, Shimonoseki, Yamaguchi 759-6595, Japan. mmiyata@fish-u.ac.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyata
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamakawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yamazoe
authors.forename: Kouichi
authors.initials: K
authors.lastname: Yoshinari
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001414:Bacitracin / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009355:Neomycin / Q000494:pharmacology; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013307:Streptomycin / Q000494:pharmacology; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013655:Taurochenodeoxycholic Acid / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D027981:Symporters; C037643:bile acid binding proteins; C476576:organic solute transporter alpha, mouse; D001414:Bacitracin; C071908:sodium-bile acid cotransporter; D013655:Taurochenodeoxycholic Acid; D000667:Ampicillin; D002790:Cholesterol 7-alpha-Hydroxylase; D009355:Neomycin; D013307:Streptomycin