Metatranscriptome of human faecal microbial communities in a cohort of adult men

Abstract

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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Fig. 1: Metatranscriptomic and metagenomic taxonomic and functional profile of a prospective human cohort.
Fig. 2: Core and variable metatranscriptomes of the stool microbiome.
Fig. 3: The gut metatranscriptome is personalized and broadly taxonomically distributed.
Fig. 4: Transcriptional landscape of the stool microbiome.
Fig. 5: Ecological interactions in the gut microbiome.
Fig. 6: Species-specific patterns of evolutionary divergence within species preserved across cohorts.

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Acknowledgements

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.

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Authors

Contributions

Study design and management were by J.I., A.T.C. and C.H. Sample collection and data generation were performed by K.L.I., D.A.D., C.D., E.R. and J.I. Data analysis was conducted by G.S.A.-A., R.S.M., J.L.-P., H.M. and T.B. Manuscript preparation and writing were conducted by G.S.A.-A., R.S.M., J.L.-P., H.M., D.A.D., J.I., A.T.C. and C.H.

Corresponding authors

Correspondence to Andrew T. Chan or Curtis Huttenhower.

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Supplementary information

Supplementary Information

Supplementary Notes, Supplementary Figures 1–5, Supplementary Figure Legends 1–10, Supplementary Table 1 and Supplementary References.

Life Sciences Reporting Summary

Supplementary Table 1

Metatranscriptomes and metagenomes.

Supplementary Table 2

Sample collection dates.

Supplementary Table 3

Taxonomic profiles.

Data set 1

Sequencing depth before and after quality filtering.

Data set 2

Community-wide and species-specific pathway transcript abundances.

Data set 3

Metagenomic pathway abundances.

Data set 4

Dispersion of pathway ECs.

Data set 5

HUMAnN2 mapping categories.

Supplementary Figure 6

Core and variable metatranscriptomes of the stool microbiome, with pathway definitions and distribution range of pathway transcript abundances.

Supplementary Figure 7

Per pathway species contributions to metagenomes and metatranscriptomes.

Supplementary Figure 8

Species-stratified distributions of metagenomic potential (DNA) and metatranscriptomic activity (RNA) for all pathways with non-zero abundance in at least 10% of samples.

Supplementary Figure 9

Ecological interactions in the gut microbiome for individual time points.

Supplementary Figure 10

Strain-level diversity is robust across cohorts.

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Abu-Ali, G.S., Mehta, R.S., Lloyd-Price, J. et al. Metatranscriptome of human faecal microbial communities in a cohort of adult men. Nat Microbiol 3, 356–366 (2018). https://doi.org/10.1038/s41564-017-0084-4

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