Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 27; pp. 16009 - 16018
• Main Authors: Zou, Ling, Spanogiannopoulos, Peter, Pieper, Lindsey M., Chien, Huan-Chieh, Cai, Wenlong, Khuri, Natalia, Pottel, Joshua, Vora, Bianca, Ni, Zhanglin, Tsakalozou, Eleftheria, Zhang, Wenjun, Shoichet, Brian K., Giacomini, Kathleen M., Turnbaugh, Peter J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 07.07.2020
• Subjects: Absorption; Additives; Animals; Anti-Allergic Agents - metabolism; Anti-Allergic Agents - pharmacokinetics; ATP Binding Cassette Transporter, Subfamily B - genetics; ATP-Binding Cassette Sub-Family B Member 4; Azo Compounds; Azo dyes; Bacteria; Bacteria - isolation & purification; Bacteria - metabolism; Biological Sciences; Community structure; Digestive system; Drug additives; Dyes; Enzymatic activity; Excipients; Excipients - metabolism; Excipients - pharmacokinetics; Female; Fexofenadine; Food; Food additives; Food Additives - metabolism; Food Additives - pharmacokinetics; Food dyes; Gastrointestinal Microbiome - physiology; Gastrointestinal tract; Genetic diversity; Gnotobiotic; Histamine H1 Antagonists, Non-Sedating - metabolism; Histamine H1 Antagonists, Non-Sedating - pharmacokinetics; Humans; Hydrophobicity; Intestinal Absorption - drug effects; Intestinal Absorption - physiology; Intestinal microflora; Intestine; Male; Metabolites; Mice; Mice, Inbred BALB C; Mice, Knockout; Microbiomes; Microorganisms; Molecular weight; Organic Anion Transporters - metabolism; Pharmacokinetics; Pharmacovigilance; Substrates; Terfenadine - analogs & derivatives; azoreductases; food additives; drug absorption; excipients; human gut microbiome

Food and drug products contain diverse and abundant small-molecule additives (excipients) with unclear impacts on human physiology, drug safety, and response. Here, we evaluate their potential impact on intestinal drug absorption. By screening 136 unique compounds for inhibition of the key intestina...