Abstract
Characterizing the stability of the gut microbiome is important to exploit it as a therapeutic target and diagnostic biomarker. We metagenomically and metatranscriptomically sequenced the faecal microbiomes of 308 participants in the Health Professionals Follow-Up Study. Participants provided four stool samples—one pair collected 24–72 h apart and a second pair ~6 months later. Within-person taxonomic and functional variation was consistently lower than between-person variation over time. In contrast, metatranscriptomic profiles were comparably variable within and between subjects due to higher within-subject longitudinal variation. Metagenomic instability accounted for ~74% of corresponding metatranscriptomic instability. The rest was probably attributable to sources such as regulation. Among the pathways that were differentially regulated, most were consistently over- or under-transcribed at each time point. Together, these results suggest that a single measurement of the faecal microbiome can provide long-term information regarding organismal composition and functional potential, but repeated or short-term measures may be necessary for dynamic features identified by metatranscriptomics.
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References
Hsiao, E. Y. et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451–1463 (2013).
Mazmanian, S. K., Round, J. L. & Kasper, D. L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620–625 (2008).
Blumberg, R. & Powrie, F. Microbiota, disease, and back to health: a metastable journey. Sci. Transl. Med. 4, 137rv7 (2012).
Caporaso, J. G. et al. Moving pictures of the human microbiome. Genome Biol. 12, R50 (2011).
Faith, J. J. et al. The long-term stability of the human gut microbiota. Science 41, 1237439 (2013).
Flores, G. E. et al. Temporal variability is a personalized feature of the human microbiome. Genome Biol. 15, 531 (2014).
Ding, T. & Schloss, P. D. Dynamics and associations of microbial community types across the human body. Nature 509, 357–360 (2014).
Jeffery, I. B., Lynch, D. B. & O’Toole, P. W. Composition and temporal stability of the gut microbiota in older persons. ISME J. 10, 170–182 (2016).
David, L. A. et al. Host lifestyle affects human microbiota on daily timescales. Genome Biol. 15, R89 (2014).
Rajilić-Stojanović, M., Heilig, H. G. H. J., Tims, S., Zoetendal, E. G. & De Vos, W. M. Long-term monitoring of the human intestinal microbiota composition. Environ. Microbiol. 15, 1146–1159 (2013).
Zoetendal, E. G., Akkermans, A. D. L. & De Vos, W. M. Temperature gradient gel electrophoresis analysis of 16S rRNA from human fecal samples reveals stable and host-specific communities of active bacteria. Appl. Environ. Microbiol. 64, 3854–3859 (1998).
Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009).
Franzosa, E. A. et al. Identifying personal microbiomes using metagenomic codes. Proc. Natl Acad. Sci. USA 112, E2930–E2938 (2015).
Dubos, R. J. & Schaedler, R. W. Reversible changes in the susceptibility of mice to bacterial infections. J. Exp. Med. 104, 53–65 (1956).
Schaedler, R. W. & Dubos, R. J. Reversible changes in the susceptibility of mice to bacterial infections. J. Exp. Med. 104, 67–84 (1956).
Schloissnig, S. et al. Genomic variation landscape of the human gut microbiome. Nature 93, 45–50 (2013).
Consortium, T. H. M. P. Structure, function and diversity of the healthy human microbiome. Nature 86, 207–214 (2012).
David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).
Dethlefsen, L. & Relman, D. A. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc. Natl Acad. Sci. USA 108, 4554–4561 (2011).
Coyte, K. Z., Schluter, J. & Foster, K. R. The ecology of the microbiome: networks, competition, and stability. Science 350, 663–666 (2015).
Franzosa, E. A. et al. Relating the metatranscriptome and metagenome of the human gut. Proc. Natl Acad. Sci. USA 111, E2329–E2338 (2014).
Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220–230 (2012).
McNulty, N. P. et al. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins. Sci. Transl. Med. 3, 106ra106 (2011).
Maurice, C. F., Haiser, H. J. & Turnbaugh, P. J. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 152, 39–50 (2013).
Abu-Ali, G. S. et al. Metatranscriptome of human faecal microbial communities in a cohort of adult men Nat. Microbiol. https://doi.org/10.1038/s41561-017-0084-4 (2018).
Abubucker, S. et al. Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLoS Comput. Biol. 8, e1002358 (2012).
Truong, D. T. et al. MetaPhlAn2 for enhanced metagenomic taxonomic profiling. Nat. Methods 12, 902–903 (2015).
Lopez-Siles, M., Duncan, S. H., Garcia-Gil, L. J. & Martinez-Medina, M. Faecalibacterium prausnitzii: from microbiology to diagnostics and prognostics. ISME J. 11, 841–852 (2017).
Mahony, J., McDonnell, B., Casey, E. & van Sinderen, D. Phage–host interactions of cheese-making lactic acid bacteria. Annu. Rev. Food Sci. Technol. 7, 267–285 (2016).
Kim, D. H., Konishi, L. & Kobashi, K. Purification, characterization and reaction mechanism of novel arylsulfotransferase obtained from an anaerobic bacterium of human intestine. Biochim. Biophys. Acta 872, 33–41 (1986).
Malojčić, G. et al. A structural and biochemical basis for PAPS-independent sulfuryl transfer by aryl sulfotransferase from uropathogenic Escherichia coli. Proc. Natl Acad. Sci. USA 105, 19217–19222 (2008).
Hehemann, J.-H. et al. Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 464, 908–912 (2010).
Jenkins, A. H., Schyns, G., Potot, S., Sun, G. & Begley, T. P. A new thiamin salvage pathway. Nat. Chem. Biol. 3, 492–497 (2007).
Bussiere, D. E. et al. Crystal structure of ErmC’, an rRNA methyltransferase which mediates antibiotic resistance in bacteria. Biochemistry 37, 7103–7112 (1998).
Jalanka, J. et al. Effects of bowel cleansing on the intestinal microbiota. Gut 64, 1562–1568 (2015).
O’Brien, C. L., Allison, G. E., Grimpen, F. & Pavli, P. Impact of colonoscopy bowel preparation on intestinal microbiota. PLoS ONE 8, e62815 (2013).
Modi, S. R., Collins, J. J. & Relman, D. A. Antibiotics and the gut microbiota. J. Clin. Invest. 124, 4212–4218 (2014).
Jakobsson, H. E. et al. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS ONE 5, e9836 (2010).
McCann, K. S. The diversity–stability debate. Nature 405, 228–233 (2000).
Schindler, D. E. et al. Population diversity and the portfolio effect in an exploited species. Nature 465, 609–612 (2010).
Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).
Lloyd-Price, J., Abu-Ali, G. & Huttenhower, C. The healthy human microbiome. Genome Med. 8, 51 (2016).
Zhernakova, A. et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352, 565–569 (2016).
Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352, 560–564 (2016).
Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010).
Lewis, S. J. & Heaton, K. W. Stool form scale as a useful guide to intestinal transit time. Scand. J. Gastroenterol. 32, 920–924 (1997).
Shishkin, A. A. et al. Simultaneous generation of many RNA-Seq libraries in a single reaction. Nat. Methods 12, 323–325 (2015).
Nakagawa, S. & Schielzeth, H. Repeatability for Gaussian and non-Gaussian data: a practical guide for biologists. Biol. Rev. 85, 935–956 (2010).
Acknowledgements
We thank the participants who graciously participated in this research, K. Stewart and G. Gupta at the Massachusetts General Hospital (MGH) who assisted with recruitment for the study, and S. Sawyer (Brigham and Women’s Hospital), M. Atar (MGH), C. Dulong (MGH and the Harvard T. H. Chan School of Public Health) and T. Poon (Broad Institut) for their assistance with project logistics, sample handling, nucleic acid extractions and sequencing. This work was supported by National Institutes of Health grants U54DE023798, UM1 CA167552, U01CA152904, R01 HL35464, R01CA202704 and K24DK098311, as well as by the Starr Cancer Consortium. A.T.C. was in part supported by the Stuart and Suzanne Steele MGH Research Scholars Program. J.I. was in part supported by the Nebraska Tobacco Settlement Biomedical Research Development Fund. R.S.M. was supported by a Howard Hughes Medical Institute Medical Research Fellowship and an AGA–Eli and Edythe Broad Student Research Fellowship.
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J.I., A.T.C. and C.H. designed and managed the study. R.S.M., D.A.D., K.L.I., G.T.B., C.D., E.B.R. and J.I. collected the samples and generated the data. R.S.M., G.S.A.-A., D.A.D., J.L.-P., A.S., P.L., A.D.J., H.K., G.T.B., M.S., L.H.N. and H.M. analysed the data. R.S.M., G.S.A.-A., D.A.D., K.L.I., J.I., C.H. and A.T.C. prepared and wrote the manuscript.
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Mehta, R.S., Abu-Ali, G.S., Drew, D.A. et al. Stability of the human faecal microbiome in a cohort of adult men. Nat Microbiol 3, 347–355 (2018). https://doi.org/10.1038/s41564-017-0096-0
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DOI: https://doi.org/10.1038/s41564-017-0096-0
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