RT Journal Article SR Electronic T1 Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives JF bioRxiv FD Cold Spring Harbor Laboratory SP 821132 DO 10.1101/821132 A1 Ling Zou A1 Peter Spanogiannopoulos A1 Huan-Chieh Chien A1 Lindsey M. Pieper A1 Wenlong Cai A1 Natalia Khuri A1 Joshua Pottel A1 Bianca Vora A1 Zhanglin Ni A1 Eleftheria Tsakalozou A1 Wenjun Zhang A1 Brian K. Shoichet A1 Kathleen M. Giacomini A1 Peter J. Turnbaugh YR 2019 UL http://biorxiv.org/content/early/2019/10/28/821132.abstract AB Food and drugs contain diverse small molecule additives (excipients) with unclear impacts on human physiology. Here, we evaluate their potential impact on intestinal absorption, screening 136 unique compounds for inhibition of the key transporter OATP2B1. We identified and validated 24 potent OATP2B1 transport inhibitors, characterized by higher molecular weight and hydrophobicity compared to poor or non-inhibitors. OATP2B1 inhibitors were also enriched for dyes, including 8 azo (R−N=N−R′) dyes. Pharmacokinetic studies in mice confirmed that FD&C Red No. 40, a common azo dye excipient, inhibited drug absorption; however, the human gut microbiome inactivated azo dye excipients, producing metabolites that no longer inhibit OATP2B1 transport. These results support a beneficial role for the microbiome in limiting the unintended effects of food and drug additives in the intestine.One Sentence Summary Food and drug additives inhibit intestinal drug transporters, although some are inactivated by gut bacterial metabolism.