ArticleProceedings of the National Academy of Sciences of the United States of America2020
Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
- Unveiling the bioactive landscape of drug inactive ingredients (DIGs) using deep transfer learning.Acta pharmaceutica Sinica. B · 2026Article
- Unraveling the complex role of intestinal microbiota in drug permeability: Insights from N-acetylcysteine.Asian journal of pharmaceutical sciences · 2026Article
- Microbiome-aware oral drug delivery: excipient-microbiome interactions and nanocarrier design rules for predictable formulation performance.Frontiers in pharmacology · 2026Review
- Food Additives Inhibit Intestinal Drug Transporters but Have Limited Effect on In Vitro Drug Permeability.Molecular pharmaceutics · 2025Article
- In Vitro Investigation of the Effects of the Food Additives Monosodium Glutamate and Allura Red AC on the human Gut Microbiota and Intestinal Cell Lines.Journal of food science · 2025Article
- Recent development of micro-nano carriers for oral antineoplastic drug delivery.Materials today. Bio · 2025Review
- Allura Red AC is a xenobiotic. Is it also a carcinogen?Carcinogenesis · 2024Review
- Simvastatin induces human gut bacterial cell surface genes.Molecular microbiology · 2024Article
- Sequence similarity network analysis of drug- and dye-modifying azoreductase enzymes found in the human gut microbiome.Archives of biochemistry and biophysics · 2024Article
- Human gut Actinobacteria boost drug absorption by secreting P-glycoprotein ATPase inhibitors.iScience · 2024Article
- Ultra-processed foods and food additives in gut health and disease.Nature reviews. Gastroenterology & hepatology · 2024Review
- Effect of Antioxidants in Medicinal Products on Intestinal Drug Transporters.Pharmaceutics · 2024Article
- Integrating the gut microbiome and pharmacology.Science translational medicine · 2024Review
- Orally Administered Drugs and Their Complicated Relationship with Our Gastrointestinal Tract.Microorganisms · 2024Review
- VARIDT 3.0: the phenotypic and regulatory variability of drug transporter.Nucleic acids research · 2024Article
- The key to intestinal health: a review and perspective on food additives.Frontiers in nutrition · 2024Review
- Dissecting the human gut microbiome to better decipher drug liability: A once-forgotten organ takes center stage.Journal of advanced research · 2023Review
- Genome-scale metabolic reconstruction of 7,302 human microorganisms for personalized medicine.Nature biotechnology · 2023Article
- Regulatory utility of physiologically based pharmacokinetic modeling for assessing food impact in bioequivalence studies: A workshop summary report.CPT: pharmacometrics & systems pharmacology · 2023Review
- Chronic exposure to synthetic food colorant Allura Red AC promotes susceptibility to experimental colitis via intestinal serotonin in mice.Nature communications · 2022Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
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 intestinal transporter OATP2B1 we identified and validated 24 potent OATP2B1 inhibitors, characterized by higher molecular weight and hydrophobicity compared to poor or noninhibitors. 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 and a potent inhibitor of OATP2B1, decreased the plasma level of the OATP2B1 substrate fexofenadine, suggesting that FD&C Red No. 40 has the potential to block drug absorption through OATP2B1 inhibition in vivo. However, the gut microbiomes of multiple unrelated healthy individuals as well as diverse human gut bacterial isolates were capable of inactivating the identified 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 and provide a framework for the data-driven selection of excipients. Furthermore, the ubiquity and genetic diversity of gut bacterial azoreductases coupled to experiments in conventionally raised and gnotobiotic mice suggest that variations in gut microbial community structure may be less important to consider relative to the high concentrations of azo dyes in food products, which have the potential to saturate gut bacterial enzymatic activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.