Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives
Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives
Abstract 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 SummaryFood and drug additives inhibit intestinal drug transporters, although some are inactivated by gut bacterial metabolism.
Giacomini Kathleen M.、Vora Bianca、Tsakalozou Eleftheria、Zhang Wenjun、Shoichet Brian K.、Zou Ling、Spanogiannopoulos Peter、Chien Huan-Chieh、Khuri Natalia、Turnbaugh Peter J.、Pieper Lindsey M.、Ni Zhanglin、Cai Wenlong、Pottel Joshua
Department of Bioengineering and Therapeutic Sciences, University of CaliforniaDepartment of Bioengineering and Therapeutic Sciences, University of CaliforniaDivision of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and ResearchDepartment of Chemical and Biomolecular Engineering, University of California||Chan Zuckerberg BiohubDepartment of Pharmaceutical Chemistry & QB3 Institute, University of CaliforniaDepartment of Bioengineering and Therapeutic Sciences, University of CaliforniaDepartment of Microbiology and Immunology, G.W. Hooper Research Foundation, University of CaliforniaDepartment of Bioengineering and Therapeutic Sciences, University of CaliforniaDepartment of Bioengineering, Stanford UniversityDepartment of Microbiology and Immunology, G.W. Hooper Research Foundation, University of California||Chan Zuckerberg BiohubDepartment of Microbiology and Immunology, G.W. Hooper Research Foundation, University of CaliforniaDivision of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and ResearchDepartment of Chemical and Biomolecular Engineering, University of CaliforniaDepartment of Pharmaceutical Chemistry & QB3 Institute, University of California
医药卫生理论药学微生物学
Giacomini Kathleen M.,Vora Bianca,Tsakalozou Eleftheria,Zhang Wenjun,Shoichet Brian K.,Zou Ling,Spanogiannopoulos Peter,Chien Huan-Chieh,Khuri Natalia,Turnbaugh Peter J.,Pieper Lindsey M.,Ni Zhanglin,Cai Wenlong,Pottel Joshua.Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives[EB/OL].(2025-03-28)[2025-06-29].https://www.biorxiv.org/content/10.1101/821132.点此复制
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