Human microbiome signatures of differential colorectal cancer drug metabolism

Leah Guthrie, Sanchit Gupta, Johanna Daily, Libusha Kelly

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

It is well appreciated that microbial metabolism of drugs can influence treatment efficacy. Microbial β-glucuronidases in the gut can reactivate the excreted, inactive metabolite of irinotecan, a first-line chemotherapeutic for metastatic colorectal cancer. Reactivation causes adverse drug responses, including severe diarrhea. However, a direct connection between irinotecan metabolism and the composition of an individual's gut microbiota has not previously been made. Here, we report quantitative evidence of inter-individual variability in microbiome metabolism of the inactive metabolite of irinotecan to its active form. We identify a high turnover microbiota metabotype with potentially elevated risk for irinotecan-dependent adverse drug responses. We link the high turnover metabotype to unreported microbial β-glucuronidases; inhibiting these enzymes may decrease irinotecan-dependent adverse drug responses in targeted subsets of patients. In total, this study reveals metagenomic mining of the microbiome, combined with metabolomics, as a non-invasive approach to develop biomarkers for colorectal cancer treatment outcomes.

Original languageEnglish (US)
Article number27
Journalnpj Biofilms and Microbiomes
Volume3
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Biotechnology
  • Microbiology
  • Applied Microbiology and Biotechnology

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