Towards a mechanistic understanding of reciprocal drug-microbiome interactions.
antibiotics
antimicrobials
human gut microbiome
metagenomics
microbial community
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
revised:
10
01
2021
received:
11
11
2020
accepted:
25
01
2021
entrez:
18
3
2021
pubmed:
19
3
2021
medline:
6
11
2021
Statut:
ppublish
Résumé
Broad-spectrum antibiotics target multiple gram-positive and gram-negative bacteria, and can collaterally damage the gut microbiota. Yet, our knowledge of the extent of damage, the antibiotic activity spectra, and the resistance mechanisms of gut microbes is sparse. This limits our ability to mitigate microbiome-facilitated spread of antibiotic resistance. In addition to antibiotics, non-antibiotic drugs affect the human microbiome, as shown by metagenomics as well as in vitro studies. Microbiome-drug interactions are bidirectional, as microbes can also modulate drugs. Chemical modifications of antibiotics mostly function as antimicrobial resistance mechanisms, while metabolism of non-antibiotics can also change the drugs' pharmacodynamic, pharmacokinetic, and toxic properties. Recent studies have started to unravel the extensive capacity of gut microbes to metabolize drugs, the mechanisms, and the relevance of such events for drug treatment. These findings raise the question whether and to which degree these reciprocal drug-microbiome interactions will differ across individuals, and how to take them into account in drug discovery and precision medicine. This review describes recent developments in the field and discusses future study areas that will benefit from systems biology approaches to better understand the mechanistic role of the human gut microbiota in drug actions.
Identifiants
pubmed: 33734582
doi: 10.15252/msb.202010116
pmc: PMC7970330
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e10116Subventions
Organisme : Medical Research Council
ID : MC_UU_00025/11
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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