Real-Time Monitoring of Host–Gut Microbial Interspecies Interaction in Anticancer Drug Metabolism

Gut microbiome can affect drug metabolism considerably, leading to modified drug response. However, quantitative estimation of host vs. microbial contributions in a living host–gut microbiome system has been challenging. Using the interspecies system of Caenorhabditis elegans and gut bacteria, we de...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2022-05, Vol.144 (19), p.8529-8535
Main Authors: Nguyen, Tin Tin Manh, Mai, Van-Hieu, Kim, Han Sun, Kim, Doyeon, Seo, Munjun, An, Yong Jin, Park, Sunghyouk
Format: Article
Language:English
Subjects:
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacology
Bacteria - metabolism
Fluorouracil - pharmacology
Gastrointestinal Microbiome
Humans
RNA, Ribosomal, 16S - genetics
RNA, Ribosomal, 16S - metabolism
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Summary:Gut microbiome can affect drug metabolism considerably, leading to modified drug response. However, quantitative estimation of host vs. microbial contributions in a living host–gut microbiome system has been challenging. Using the interspecies system of Caenorhabditis elegans and gut bacteria, we developed a real-time approach for monitoring their metabolic interaction in vivo during anticancer drug 5-fluorouracil (5-FU) metabolism. The fluorine NMR-based approach yielded the quantitative contributions to the host 5-FU metabolism made by human gut-microbial species of variable genetic backgrounds. It also experimentally confirmed a bacterial gene–metabolism relationship. Differential 5-FU catabolism among bacterial substrains and the contributions to the host metabolism, unobservable by conventional 16S rRNA metagenomic sequencing, were also found. The metabolic contributions could be correlated with phenotypic developmental toxicity of 5-FU to the host fed with different substrains. Our convenient platform should help to reveal heterogeneity in host–gut microbiome interactions for many drugs in a living symbiotic system.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.1c10998