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

Ian H McHardy1, Maryam Goudarzi3, Maomeng Tong8, Paul M Ruegger4, Emma Schwager7, John R Weger4, Thomas G Graeber8, Justin L Sonnenburg6, Steve Horvath5, Curtis Huttenhower7, Dermot PB McGovern2, Albert J Fornace3, James Borneman4 and Jonathan Braun1*

Author Affiliations

1 Pathology and Laboratory Medicine UCLA, Los Angeles, CA, USA

2 The F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedar's Sinai Medical Center, Los Angeles, CA, USA

3 Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC, USA

4 Plant Pathology, UC Riverside, Riverside, CA, USA

5 Biostatistics, UCLA, Los Angeles, CA, USA

6 Microbiology and Immunology, Stanford University, Palo Alto, CA, USA

7 Biostatistics, Harvard University, Boston, MA, USA

8 Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USA

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Microbiome 2013, 1:17  doi:10.1186/2049-2618-1-17

Published: 5 June 2013

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.

Keywords:
Microbiome; Metabolome; Inter-omic analysis