The gut microbiome is intimately related to human health, but it is not yet known which functional activities are driven by specific microorganisms' ecological configurations or transcription. We report a large-scale investigation of 372 human faecal metatranscriptomes and 929 metagenomes from a subset of 308 men in the Health Professionals Follow-Up Study. We identified a metatranscriptomic 'core' universally transcribed over time and across participants, often by different microorganisms. In contrast to the housekeeping functions enriched in this core, a 'variable' metatranscriptome included specialized pathways that were differentially expressed both across participants and among microorganisms. Finally, longitudinal metagenomic profiles allowed ecological interaction network reconstruction, which remained stable over the six-month timespan, as did strain tracking within and between participants. These results provide an initial characterization of human faecal microbial ecology into core, subject-specific, microorganism-specific and temporally variable transcription, and they differentiate metagenomically versus metatranscriptomically informative aspects of the human faecal microbiome.
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We thank the participants in the MLVS and the HMP who graciously contributed to this research. This work was supported by funding from STARR Cancer Consortium Award no. I7-A714 to C.H., NCI R01CA202704 (A.T.C., C.H. and J.I.), NIDDK DK098311 (A.T.C.), and NIDDK U54DE023798 (C.H.). J.I. is further supported by Nebraska Tobacco Settlement Biomedical Research Development Funds. K.L.I. is supported by the National Health and Medical Research Council. Components of the Men’s Lifestyle Validation Study were supported by NCI U01CA152904 and UM1 CA167552. R.S.M. is supported by a Howard Hughes Medical Institute Fellowship Award. We are also grateful for initial pilot funding provided by B. Wu and E. Larsen. A.T.C. is a Stuart and Suzanne Steele MGH Research Scholar.
Supplementary Notes, Supplementary Figures 1–5, Supplementary Figure Legends 1–10, Supplementary Table 1 and Supplementary References.
Metatranscriptomes and metagenomes.
Sample collection dates.
Sequencing depth before and after quality filtering.
Community-wide and species-specific pathway transcript abundances.
Metagenomic pathway abundances.
Dispersion of pathway ECs.
HUMAnN2 mapping categories.
Core and variable metatranscriptomes of the stool microbiome, with pathway definitions and distribution range of pathway transcript abundances.
Per pathway species contributions to metagenomes and metatranscriptomes.
Species-stratified distributions of metagenomic potential (DNA) and metatranscriptomic activity (RNA) for all pathways with non-zero abundance in at least 10% of samples.
Ecological interactions in the gut microbiome for individual time points.
Strain-level diversity is robust across cohorts.