한빛사 논문
서울대학교 약학대학
Tin Tin Manh Nguyen†, Van-Hieu Mai†, Han Sun Kim, Doyeon Kim, Munjun Seo, Yong Jin An*, Sunghyouk Park*
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Korea
†T.T.M.N. and V.-H.M. contributed equally to this work.
*Corresponding author.
Abstract
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.
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