The human gut chemical landscape predicts microbe-mediated biotransformation of foods and drugs

Leah Guthrie, Sarah Wolfson, Libusha Kelly

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Microbes are nature's chemists, capable of producing and metabolizing a diverse array of compounds. In the human gut, microbial biochemistry can be beneficial, for example vitamin production and complex carbohydrate breakdown; or detrimental, such as the reactivation of an inactive drug metabolite leading to patient toxicity. Identifying clinically relevant microbiome metabolism requires linking microbial biochemistry and ecology with patient outcomes. Here we present MicrobeFDT, a resource which clusters chemically similar drug and food compounds and links these compounds to microbial enzymes and known toxicities. We demonstrate that compound structural similarity can serve as a proxy for toxicity, enzyme sharing, and coarse-grained functional similarity. MicrobeFDT allows users to flexibly interrogate microbial metabolism, compounds of interest, and toxicity profiles to generate novel hypotheses of microbe-diet-drug-phenotype interactions that influence patient outcomes. We validate one such hypothesis experimentally, using MicrobeFDT to reveal unrecognized gut microbiome metabolism of the ovarian cancer drug altretamine.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Jun 11 2019

Fingerprint

Biotransformation
Toxicity
Metabolism
Food
Biochemistry
Altretamine
Pharmaceutical Preparations
Microbiota
Drug interactions
Proxy
Enzymes
Ecology
Drug Interactions
Vitamins
Ovarian Neoplasms
Nutrition
Metabolites
Carbohydrates
Diet
Phenotype

Keywords

  • biochemistry
  • chemical biology
  • chemical landscape
  • gut microbiome
  • human
  • infectious disease
  • microbial metabolism
  • microbiology

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

The human gut chemical landscape predicts microbe-mediated biotransformation of foods and drugs. / Guthrie, Leah; Wolfson, Sarah; Kelly, Libusha.

In: eLife, Vol. 8, 11.06.2019.

Research output: Contribution to journalArticle

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