Human microbiome signatures of differential colorectal cancer drug metabolism

Leah Guthrie, Sanchit Gupta, Johanna P. Daily, Libusha Kelly

Research output: Contribution to journalArticle

29 Citations (Scopus)

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

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irinotecan
Microbiota
Colorectal Neoplasms
Pharmaceutical Preparations
Glucuronidase
Metagenomics
Metabolomics
Diarrhea
Biomarkers

ASJC Scopus subject areas

  • Biotechnology
  • Microbiology
  • Applied Microbiology and Biotechnology

Cite this

Human microbiome signatures of differential colorectal cancer drug metabolism. / Guthrie, Leah; Gupta, Sanchit; Daily, Johanna P.; Kelly, Libusha.

In: npj Biofilms and Microbiomes, Vol. 3, No. 1, 27, 01.12.2017.

Research output: Contribution to journalArticle

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