دورية أكاديمية
أعرض في EDS

Human gut Actinobacteria boost drug absorption by secreting P-glycoprotein ATPase inhibitors.

التفاصيل البيبلوغرافية
العنوان: Human gut Actinobacteria boost drug absorption by secreting P-glycoprotein ATPase inhibitors.
المؤلفون: Kyaw TS; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Zhang C; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Sandy M; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA.; Quantitative Metabolite Analysis Center, Benioff Center for Microbiome Medicine, University of California San Francisco, San Francisco, CA 94143, USA., Trepka K; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Zhang S; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Ramirez Hernandez LA; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Ramirez L; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Goh JJN; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Yu K; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Dimassa V; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Bess EN; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Brockert JG; Quantitative Metabolite Analysis Center, Benioff Center for Microbiome Medicine, University of California San Francisco, San Francisco, CA 94143, USA., Dumlao DS; Quantitative Metabolite Analysis Center, Benioff Center for Microbiome Medicine, University of California San Francisco, San Francisco, CA 94143, USA., Bisanz JE; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Turnbaugh PJ; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA.; Chan-Zuckerberg Biohub-San Francisco, San Francisco, CA 94158, USA.
المصدر: IScience [iScience] 2024 May 27; Vol. 27 (6), pp. 110122. Date of Electronic Publication: 2024 May 27 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2018]-
مستخلص: Drug efflux transporters are a major determinant of drug efficacy and toxicity. A canonical example is P-glycoprotein (P-gp), an efflux transporter that controls the intestinal absorption of diverse compounds. Despite a rich literature on the dietary and pharmaceutical compounds that impact P-gp activity, its sensitivity to gut microbial metabolites remains an open question. Surprisingly, we found that the cardiac drug-metabolizing gut Actinobacterium Eggerthella lenta increases drug absorption in mice. Experiments in cell culture revealed that E. lenta produces a soluble factor that post-translationally inhibits P-gp ATPase efflux activity. P-gp inhibition is conserved in the Eggerthellaceae family but absent in other Actinobacteria. Comparative genomics identified genes associated with P-gp inhibition. Finally, activity-guided biochemical fractionation coupled to metabolomics implicated a group of small polar metabolites with P-gp inhibitory activity. These results highlight the importance of considering the broader relevance of the gut microbiome for drug disposition beyond first-pass metabolism.
Competing Interests: P.J.T. is on the scientific advisory boards for Pendulum, Seres, and SNIPR Biome; there is no direct overlap between the current study and these consulting duties.
(© 2024 The Author(s).)
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فهرسة مساهمة: Keywords: Biological sciences; Microbiology; Microbiome; Natural sciences; Pharmacology
تواريخ الأحداث: Date Created: 20240701 Latest Revision: 20240702
رمز التحديث: 20240702
مُعرف محوري في PubMed: PMC11214321
DOI: 10.1016/j.isci.2024.110122
PMID: 38947502
قاعدة البيانات: MEDLINE
الوصف
تدمد:2589-0042
DOI:10.1016/j.isci.2024.110122