Integrative analysis of the microbiome and metabolome of the human intestinal mucosal surface reveals exquisite inter-relationships

Ian Howard Mchardy, Maryam Goudarzi, Maomeng Tong, Paul M. Ruegger, Emma Schwager, John R. Weger, Thomas G. Graeber, Justin L. Sonnenburg, Steve Horvath, Curtis Huttenhower, Dermot P B McGovern, Albert J. Fornace, James Borneman, Jonathan Braun

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Background: Consistent compositional shifts in the gut microbiota are observed in IBD and other chronic intestinal disorders and may contribute to pathogenesis. The identities of microbial biomolecular mechanisms and metabolic products responsible for disease phenotypes remain to be determined, as do the means by which such microbial functions may be therapeutically modified. Results: The composition of the microbiota and metabolites in gut microbiome samples in 47 subjects were determined. Samples were obtained by endoscopic mucosal lavage from the cecum and sigmoid colon regions, and each sample was sequenced using the 16S rRNA gene V4 region (Illumina-HiSeq 2000 platform) and assessed by UPLC mass spectroscopy. Spearman correlations were used to identify widespread, statistically significant microbial-metabolite relationships. Metagenomes for identified microbial OTUs were imputed using PICRUSt, and KEGG metabolic pathway modules for imputed genes were assigned using HUMAnN. The resulting metabolic pathway abundances were mostly concordant with metabolite data. Analysis of the metabolome-driven distribution of OTU phylogeny and function revealed clusters of clades that were both metabolically and metagenomically similar. Conclusions: The results suggest that microbes are syntropic with mucosal metabolome composition and therefore may be the source of and/or dependent upon gut epithelial metabolites. The consistent relationship between inferred metagenomic function and assayed metabolites suggests that metagenomic composition is predictive to a reasonable degree of microbial community metabolite pools. The finding that certain metabolites strongly correlate with microbial community structure raises the possibility of targeting metabolites for monitoring and/or therapeutically manipulating microbial community function in IBD and other chronic diseases.

Original languageEnglish (US)
Article number17
JournalMicrobiome
Volume1
Issue number1
DOIs
StatePublished - Jun 5 2013

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Metagenomics
Metabolome
Microbiota
Metabolic Networks and Pathways
Metagenome
Cecum
Gene Regulatory Networks
Therapeutic Irrigation
Sigmoid Colon
Phylogeny
rRNA Genes
Mass Spectrometry
Chronic Disease
Phenotype
Gastrointestinal Microbiome

Keywords

  • Inter-omic analysis
  • Metabolome
  • Microbiome

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

Integrative analysis of the microbiome and metabolome of the human intestinal mucosal surface reveals exquisite inter-relationships. / Mchardy, Ian Howard; Goudarzi, Maryam; Tong, Maomeng; Ruegger, Paul M.; Schwager, Emma; Weger, John R.; Graeber, Thomas G.; Sonnenburg, Justin L.; Horvath, Steve; Huttenhower, Curtis; McGovern, Dermot P B; Fornace, Albert J.; Borneman, James; Braun, Jonathan.

In: Microbiome, Vol. 1, No. 1, 17, 05.06.2013.

Research output: Contribution to journalArticle

Mchardy, IH, Goudarzi, M, Tong, M, Ruegger, PM, Schwager, E, Weger, JR, Graeber, TG, Sonnenburg, JL, Horvath, S, Huttenhower, C, McGovern, DPB, Fornace, AJ, Borneman, J & Braun, J 2013, 'Integrative analysis of the microbiome and metabolome of the human intestinal mucosal surface reveals exquisite inter-relationships', Microbiome, vol. 1, no. 1, 17. https://doi.org/10.1186/2049-2618-1-17
Mchardy, Ian Howard ; Goudarzi, Maryam ; Tong, Maomeng ; Ruegger, Paul M. ; Schwager, Emma ; Weger, John R. ; Graeber, Thomas G. ; Sonnenburg, Justin L. ; Horvath, Steve ; Huttenhower, Curtis ; McGovern, Dermot P B ; Fornace, Albert J. ; Borneman, James ; Braun, Jonathan. / Integrative analysis of the microbiome and metabolome of the human intestinal mucosal surface reveals exquisite inter-relationships. In: Microbiome. 2013 ; Vol. 1, No. 1.
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abstract = "Background: Consistent compositional shifts in the gut microbiota are observed in IBD and other chronic intestinal disorders and may contribute to pathogenesis. The identities of microbial biomolecular mechanisms and metabolic products responsible for disease phenotypes remain to be determined, as do the means by which such microbial functions may be therapeutically modified. Results: The composition of the microbiota and metabolites in gut microbiome samples in 47 subjects were determined. Samples were obtained by endoscopic mucosal lavage from the cecum and sigmoid colon regions, and each sample was sequenced using the 16S rRNA gene V4 region (Illumina-HiSeq 2000 platform) and assessed by UPLC mass spectroscopy. Spearman correlations were used to identify widespread, statistically significant microbial-metabolite relationships. Metagenomes for identified microbial OTUs were imputed using PICRUSt, and KEGG metabolic pathway modules for imputed genes were assigned using HUMAnN. The resulting metabolic pathway abundances were mostly concordant with metabolite data. Analysis of the metabolome-driven distribution of OTU phylogeny and function revealed clusters of clades that were both metabolically and metagenomically similar. Conclusions: The results suggest that microbes are syntropic with mucosal metabolome composition and therefore may be the source of and/or dependent upon gut epithelial metabolites. The consistent relationship between inferred metagenomic function and assayed metabolites suggests that metagenomic composition is predictive to a reasonable degree of microbial community metabolite pools. The finding that certain metabolites strongly correlate with microbial community structure raises the possibility of targeting metabolites for monitoring and/or therapeutically manipulating microbial community function in IBD and other chronic diseases.",
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AU - Tong, Maomeng

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AU - Schwager, Emma

AU - Weger, John R.

AU - Graeber, Thomas G.

AU - Sonnenburg, Justin L.

AU - Horvath, Steve

AU - Huttenhower, Curtis

AU - McGovern, Dermot P B

AU - Fornace, Albert J.

AU - Borneman, James

AU - Braun, Jonathan

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N2 - Background: Consistent compositional shifts in the gut microbiota are observed in IBD and other chronic intestinal disorders and may contribute to pathogenesis. The identities of microbial biomolecular mechanisms and metabolic products responsible for disease phenotypes remain to be determined, as do the means by which such microbial functions may be therapeutically modified. Results: The composition of the microbiota and metabolites in gut microbiome samples in 47 subjects were determined. Samples were obtained by endoscopic mucosal lavage from the cecum and sigmoid colon regions, and each sample was sequenced using the 16S rRNA gene V4 region (Illumina-HiSeq 2000 platform) and assessed by UPLC mass spectroscopy. Spearman correlations were used to identify widespread, statistically significant microbial-metabolite relationships. Metagenomes for identified microbial OTUs were imputed using PICRUSt, and KEGG metabolic pathway modules for imputed genes were assigned using HUMAnN. The resulting metabolic pathway abundances were mostly concordant with metabolite data. Analysis of the metabolome-driven distribution of OTU phylogeny and function revealed clusters of clades that were both metabolically and metagenomically similar. Conclusions: The results suggest that microbes are syntropic with mucosal metabolome composition and therefore may be the source of and/or dependent upon gut epithelial metabolites. The consistent relationship between inferred metagenomic function and assayed metabolites suggests that metagenomic composition is predictive to a reasonable degree of microbial community metabolite pools. The finding that certain metabolites strongly correlate with microbial community structure raises the possibility of targeting metabolites for monitoring and/or therapeutically manipulating microbial community function in IBD and other chronic diseases.

AB - Background: Consistent compositional shifts in the gut microbiota are observed in IBD and other chronic intestinal disorders and may contribute to pathogenesis. The identities of microbial biomolecular mechanisms and metabolic products responsible for disease phenotypes remain to be determined, as do the means by which such microbial functions may be therapeutically modified. Results: The composition of the microbiota and metabolites in gut microbiome samples in 47 subjects were determined. Samples were obtained by endoscopic mucosal lavage from the cecum and sigmoid colon regions, and each sample was sequenced using the 16S rRNA gene V4 region (Illumina-HiSeq 2000 platform) and assessed by UPLC mass spectroscopy. Spearman correlations were used to identify widespread, statistically significant microbial-metabolite relationships. Metagenomes for identified microbial OTUs were imputed using PICRUSt, and KEGG metabolic pathway modules for imputed genes were assigned using HUMAnN. The resulting metabolic pathway abundances were mostly concordant with metabolite data. Analysis of the metabolome-driven distribution of OTU phylogeny and function revealed clusters of clades that were both metabolically and metagenomically similar. Conclusions: The results suggest that microbes are syntropic with mucosal metabolome composition and therefore may be the source of and/or dependent upon gut epithelial metabolites. The consistent relationship between inferred metagenomic function and assayed metabolites suggests that metagenomic composition is predictive to a reasonable degree of microbial community metabolite pools. The finding that certain metabolites strongly correlate with microbial community structure raises the possibility of targeting metabolites for monitoring and/or therapeutically manipulating microbial community function in IBD and other chronic diseases.

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