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<p>For orally administered drugs, intestinal first-pass metabolism influences systemic exposure and accounts for inter-individual pharmacokinetic differences. However, the mechanistic roles of gut microbiome-mediated biotransformation and patient-specific intestinal variability remain underrepresented in current regulatory frameworks. This Perspective explores how human-relevant culturomics platforms, including Gut-on-a-Chip microphysiological systems, allow for quantitative analysis of host-microbiome-drug interactions. We also discuss the potential of predictive intestinal ecosystem models for personalized pharmacomicrobiomics and next-generation translational drug development.</p>

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Engineering human Gut-on-a-Chip culturomics for predictive pharmacomicrobiomics of first-pass metabolism

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月23日

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  • Itsuma Nagao,
  • Hyun Jung Kim

摘要

For orally administered drugs, intestinal first-pass metabolism influences systemic exposure and accounts for inter-individual pharmacokinetic differences. However, the mechanistic roles of gut microbiome-mediated biotransformation and patient-specific intestinal variability remain underrepresented in current regulatory frameworks. This Perspective explores how human-relevant culturomics platforms, including Gut-on-a-Chip microphysiological systems, allow for quantitative analysis of host-microbiome-drug interactions. We also discuss the potential of predictive intestinal ecosystem models for personalized pharmacomicrobiomics and next-generation translational drug development.