Relating the metatranscriptome and metagenome of the human gut.

Proc Natl Acad Sci U S A

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 metatranscriptome 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.

Year of Publication
Proc Natl Acad Sci U S A
Date Published
2014 Jun 03
PubMed ID
PubMed Central ID
Grant list
R01 CA166150 / CA / NCI NIH HHS / United States
U54 DK102557 / DK / NIDDK NIH HHS / United States
HHSN272200900018C / AI / NIAID NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
R01 CA137178 / CA / NCI NIH HHS / United States
P30 DK034854 / DK / NIDDK NIH HHS / United States
R01 CA154426 / CA / NCI NIH HHS / United States
HHSN272200900018C / PHS HHS / United States
R01 HG005969 / HG / NHGRI NIH HHS / United States
CA166150 / CA / NCI NIH HHS / United States
P50 CA127003 / CA / NCI NIH HHS / United States
U19 AI110818 / AI / NIAID NIH HHS / United States