PT  - JOURNAL ARTICLE
AU  - Ling Zou
AU  - Peter Spanogiannopoulos
AU  - Huan-Chieh Chien
AU  - Lindsey M. Pieper
AU  - Wenlong Cai
AU  - Natalia Khuri
AU  - Joshua Pottel
AU  - Bianca Vora
AU  - Zhanglin Ni
AU  - Eleftheria Tsakalozou
AU  - Wenjun Zhang
AU  - Brian K. Shoichet
AU  - Kathleen M. Giacomini
AU  - Peter J. Turnbaugh
TI  - Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives
AID  - 10.1101/821132
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 821132
4099  - http://biorxiv.org/content/early/2019/10/28/821132.short
4100  - http://biorxiv.org/content/early/2019/10/28/821132.full
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.