Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives
Open accessPublished version of a preprint
Abstract
Significance: Food and drug products are supplemented with small molecules called excipients that are assumed to be inert. In this study, we screened a collection of common oral excipients and identified 24 that inhibit intestinal drug transport, including the common excipient FD&C Red No. 40, which decreased drug absorption in mice. Excipient inhibitors were enriched for azo dyes, which human gut bacteria could metabolize, producing metabolites that no longer inhibit intestinal drug transporter activity. This work demonstrates the unintended consequences of oral excipients and a beneficial role for the gut microbiome in limiting these unfavorable effects.
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Cites
Kennedy, E. A., King, K. Y., & Baldridge, M. T. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01534 · Cited by 602 · see citing works
Gut reactions: Breaking down xenobiotic–microbiome interactions
Clarke, G., Sandhu, K. V., Griffin, B. T., Dinan, T. G., Cryan, J. F., & Hyland, N. P. (2019) · Pharmacological Reviews · doi:10.1124/pr.118.015768 · Cited by 319 · see citing works
Intestinal Microbiota Regulate Xenobiotic Metabolism in the Liver
Björkholm, B., Bok, C. M., Lundin, A., Rafter, J., Hibberd, M. L., & Pettersson, S. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006958 · Cited by 249 · see citing works
Developing a metagenomic view of xenobiotic metabolism
Haiser, H. J., & Turnbaugh, P. J. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2012.07.009 · Cited by 186 · see citing works
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A data-driven approach for predicting the impact of drugs on the human microbiome
Algavi, Y. M., & Borenstein, E. (2023) · Nature Communications · doi:10.1038/s41467-023-39264-0 · Cited by 54 · see citing works
- Authors
- Zou, L., Spanogiannopoulos, P., Pieper, L. M., Chien, H.-C., Cai, W., Khuri, N., Pottel, J., Vora, B., Ni, Z., Tsakalozou, E., Zhang, W., Shoichet, B. K., Giacomini, K. M., & Turnbaugh, P. J.
- Affiliations
- University of California, San Francisco (US)
- University of California, Berkeley (US)
- Stanford University (US)
- QB3 (US)
- United States Food and Drug Administration (US)
- Chan Zuckerberg Biohub San Francisco (US)
- Corresponding author
- Giacomini, Kathleen M.
- Turnbaugh, Peter J.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-06-22
- Volume
- 117
- Issue
- 27
- Pages
- 16009-16018
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC7355017
- OpenAlex
- W3035779321
- Cited by
- 61
- References
- 4
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 12 · 2023: 10 · 2022: 13 · 2021: 8 · 2020: 4
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- HHS | U.S. Food and Drug Administration (U01FD004979, U01FD005978)
- HHS | NIH | National Heart, Lung, and Blood Institute (R01HL122593)
- HHS | NIH | National Cancer Institute (R21CA227232)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Physical Sciences › Chemistry › Analytical Chemistry › Dye analysis and toxicity
- Keywords
- OATP2B1, intestinal drug absorption, pharmaceutical excipients, azo dyes, gut microbiota, drug-metabolizing enzymes, fexofenadine, drug-drug interactions, gnotobiotic mice
- MeSH terms
- Gastrointestinal Microbiome, ATP-Binding Cassette Sub-Family B Member 4, Animals, Azo Compounds, Bacteria, Excipients, Female, Food, Food Additives, Humans, Intestinal Absorption, Male, Mice, Inbred BALB C, Terfenadine, Mice, Knockout, ATP Binding Cassette Transporter, Subfamily B, Anti-Allergic Agents, Organic Anion Transporters, Histamine H1 Antagonists, Non-Sedating, Mice
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