The Parkinson's disease drug entacapone disrupts gut microbiome homoeostasis via iron sequestration.

Autor: Pereira FC; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria. f.c.pereira@soton.ac.uk.; School of Biological Sciences, University of Southampton, Southampton, UK. f.c.pereira@soton.ac.uk., Ge X; Department of Electrical and Computer Engineering, Boston University, Boston, MA, USA., Kristensen JM; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria., Kirkegaard RH; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria.; Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna, Vienna, Austria., Maritsch K; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria., Szamosvári D; Department of Biological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria., Imminger S; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria., Seki D; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria., Shazzad JB; School of Biological Sciences, University of Southampton, Southampton, UK., Zhu Y; Department of Chemistry, Boston University, Boston, MA, USA., Decorte M; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria., Hausmann B; Department of Biological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria., Berry D; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria., Wasmund K; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria.; School of Biological Sciences, University of Portsmouth, Portsmouth, UK., Schintlmeister A; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria., Böttcher T; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria.; Department of Biological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria., Cheng JX; Department of Electrical and Computer Engineering, Boston University, Boston, MA, USA. jxcheng@bu.edu.; Department of Biomedical Engineering, Photonics Center, Boston University, Boston, MA, USA. jxcheng@bu.edu., Wagner M; Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria. michael.wagner@univie.ac.at.; Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark. michael.wagner@univie.ac.at.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2024 Dec; Vol. 9 (12), pp. 3165-3183. Date of Electronic Publication: 2024 Nov 21.
DOI: 10.1038/s41564-024-01853-0
Abstrakt: Many human-targeted drugs alter the gut microbiome, leading to implications for host health. However, the mechanisms underlying these effects are not well known. Here we combined quantitative microbiome profiling, long-read metagenomics, stable isotope probing and single-cell chemical imaging to investigate the impact of two widely prescribed drugs on the gut microbiome. Physiologically relevant concentrations of entacapone, a treatment for Parkinson's disease, or loxapine succinate, used to treat schizophrenia, were incubated ex vivo with human faecal samples. Both drugs significantly impact microbial activity, more so than microbial abundance. Mechanistically, entacapone can complex and deplete available iron resulting in gut microbiome composition and function changes. Microbial growth can be rescued by replenishing levels of microbiota-accessible iron. Further, entacapone-induced iron starvation selected for iron-scavenging gut microbiome members encoding antimicrobial resistance and virulence genes. These findings reveal the impact of two under-investigated drugs on whole microbiomes and identify metal sequestration as a mechanism of drug-induced microbiome disturbance.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. Crown.)
Databáze: MEDLINE
Externí odkaz: