Relating the metatranscriptome and metagenome of the human gut

Eric A. Franzosa, Xochitl C. Morgan, Nicola Segata, Levi Waldron, Joshua Reyes, Ashlee M. Earl, Georgia Giannoukos, Matthew R. Boylan, Dawn Ciulla, Dirk Gevers, Jacques Izard, Wendy S. Garrett, Andrew T. Chan, Curtis Huttenhower

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223 Citations (Scopus)

Abstract

Although the composition of the human microbiome is now well-studied, the microbiota's >8 million genes and their regulation remain largely uncharacterized. This knowledge gap is in part because of the difficulty of acquiring large numbers of samples amenable to functional studies of the microbiota. We conducted what is, to our knowledge, one of the first human microbiome studies in a well-phenotyped prospective cohort incorporating taxonomic, metagenomic, and metatranscriptomic profiling at multiple body sites using self-collected samples. Stool and saliva were provided by eight healthy subjects, with the former preserved by three different methods (freezing, ethanol, and RNAlater) to validate self-collection. Within-subject microbial species, gene, and transcript abundances were highly concordant across sampling methods, with only a small fraction of transcripts ( <5%) displaying between-method variation. Next, we investigated relationships between the oral and gut microbial communities, identifying a subset of abundant oral microbes that routinely survive transit to the gut, but with minimal transcriptional activity there. Finally, systematic comparison of the gut metagenome and meta-transcriptome revealed that a substantial fraction (41%) of microbial transcripts were not differentially regulated relative to their genomic abundances. Of the remainder, consistently underexpressed pathways included sporulation and amino acid biosynthesis, whereas up-regulated pathways included ribosome biogenesis and methanogenesis. Across subjects, metatranscriptional profiles were significantly more individualized than DNA-level functional profiles, but less variable than microbial composition, indicative of subject-specific whole-community regulation. The results thus detail relationships between community genomic potential and gene expression in the gut, and establish the feasibility of metatranscriptomic investigations in subject-collected and shipped samples.

Original languageEnglish (US)
Pages (from-to)E2329-E2338
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number22
DOIs
StatePublished - Jun 3 2014

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Metagenome
Microbiota
Metagenomics
Microbial Genes
Ribosomes
Transcriptome
Saliva
Freezing
Healthy Volunteers
Ethanol
Gene Expression
Amino Acids
DNA
Genes

ASJC Scopus subject areas

  • General

Cite this

Franzosa, E. A., Morgan, X. C., Segata, N., Waldron, L., Reyes, J., Earl, A. M., ... Huttenhower, C. (2014). Relating the metatranscriptome and metagenome of the human gut. Proceedings of the National Academy of Sciences of the United States of America, 111(22), E2329-E2338. https://doi.org/10.1073/pnas.1319284111

Relating the metatranscriptome and metagenome of the human gut. / Franzosa, Eric A.; Morgan, Xochitl C.; Segata, Nicola; Waldron, Levi; Reyes, Joshua; Earl, Ashlee M.; Giannoukos, Georgia; Boylan, Matthew R.; Ciulla, Dawn; Gevers, Dirk; Izard, Jacques; Garrett, Wendy S.; Chan, Andrew T.; Huttenhower, Curtis.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 22, 03.06.2014, p. E2329-E2338.

Research output: Contribution to journalArticle

Franzosa, EA, Morgan, XC, Segata, N, Waldron, L, Reyes, J, Earl, AM, Giannoukos, G, Boylan, MR, Ciulla, D, Gevers, D, Izard, J, Garrett, WS, Chan, AT & Huttenhower, C 2014, 'Relating the metatranscriptome and metagenome of the human gut', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 22, pp. E2329-E2338. https://doi.org/10.1073/pnas.1319284111
Franzosa, Eric A. ; Morgan, Xochitl C. ; Segata, Nicola ; Waldron, Levi ; Reyes, Joshua ; Earl, Ashlee M. ; Giannoukos, Georgia ; Boylan, Matthew R. ; Ciulla, Dawn ; Gevers, Dirk ; Izard, Jacques ; Garrett, Wendy S. ; Chan, Andrew T. ; Huttenhower, Curtis. / Relating the metatranscriptome and metagenome of the human gut. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 22. pp. E2329-E2338.
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