A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice

A. Marcobal, Purna C Kashyap, T. A. Nelson, P. A. Aronov, M. S. Donia, A. Spormann, M. A. Fischbach, J. L. Sonnenburg

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

Defining the functional status of host-associated microbial ecosystems has proven challenging owing to the vast number of predicted genes within the microbiome and relatively poor understanding of community dynamics and community-host interaction. Metabolomic approaches, in which a large number of small molecule metabolites can be defined in a biological sample, offer a promising avenue to 'fingerprint' microbiota functional status. Here, we examined the effects of the human gut microbiota on the fecal and urinary metabolome of a humanized (HUM) mouse using an optimized ultra performance liquid chromatography-mass spectrometry-based method. Differences between HUM and conventional mouse urine and fecal metabolomic profiles support host-specific aspects of the microbiota's metabolomic contribution, consistent with distinct microbial compositions. Comparison of microbiota composition and metabolome of mice humanized with different human donors revealed that the vast majority of metabolomic features observed in donor samples are produced in the corresponding HUM mice, and individual-specific features suggest 'personalized' aspects of functionality can be reconstituted in mice. Feeding the mice a defined, custom diet resulted in modification of the metabolite signatures, illustrating that host diet provides an avenue for altering gut microbiota functionality, which in turn can be monitored via metabolomics. Using a defined model microbiota consisting of one or two species, we show that simplified communities can drive major changes in the host metabolomic profile. Our results demonstrate that metabolomics constitutes a powerful avenue for functional characterization of the intestinal microbiota and its interaction with the host.

Original languageEnglish (US)
Pages (from-to)1933-1943
Number of pages11
JournalISME Journal
Volume7
Issue number10
DOIs
StatePublished - Oct 2013

Fingerprint

Germ-Free Life
metabolome
Metabolomics
Metabolome
metabolomics
intestinal microorganisms
Microbiota
mice
functional status
metabolite
diet
metabolites
Diet
community dynamics
ultra-performance liquid chromatography
microbial ecology
urine
Dermatoglyphics
Gastrointestinal Microbiome
liquid chromatography

Keywords

  • Gut microbiota
  • Humanized mice
  • Metabolomics
  • UPLC-MS

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Microbiology

Cite this

Marcobal, A., Kashyap, P. C., Nelson, T. A., Aronov, P. A., Donia, M. S., Spormann, A., ... Sonnenburg, J. L. (2013). A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice. ISME Journal, 7(10), 1933-1943. https://doi.org/10.1038/ismej.2013.89

A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice. / Marcobal, A.; Kashyap, Purna C; Nelson, T. A.; Aronov, P. A.; Donia, M. S.; Spormann, A.; Fischbach, M. A.; Sonnenburg, J. L.

In: ISME Journal, Vol. 7, No. 10, 10.2013, p. 1933-1943.

Research output: Contribution to journalArticle

Marcobal, A, Kashyap, PC, Nelson, TA, Aronov, PA, Donia, MS, Spormann, A, Fischbach, MA & Sonnenburg, JL 2013, 'A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice', ISME Journal, vol. 7, no. 10, pp. 1933-1943. https://doi.org/10.1038/ismej.2013.89
Marcobal, A. ; Kashyap, Purna C ; Nelson, T. A. ; Aronov, P. A. ; Donia, M. S. ; Spormann, A. ; Fischbach, M. A. ; Sonnenburg, J. L. / A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice. In: ISME Journal. 2013 ; Vol. 7, No. 10. pp. 1933-1943.
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