Early life dynamics of the human gut virome and bacterial microbiome in infants


The early years of life are important for immune development and influence health in adulthood. Although it has been established that the gut bacterial microbiome is rapidly acquired after birth, less is known about the viral microbiome (or 'virome'), consisting of bacteriophages and eukaryotic RNA and DNA viruses, during the first years of life. Here, we characterized the gut virome and bacterial microbiome in a longitudinal cohort of healthy infant twins. The virome and bacterial microbiome were more similar between co-twins than between unrelated infants. From birth to 2 years of age, the eukaryotic virome and the bacterial microbiome expanded, but this was accompanied by a contraction of and shift in the bacteriophage virome composition. The bacteriophage-bacteria relationship begins from birth with a high predator–low prey dynamic, consistent with the Lotka-Volterra prey model. Thus, in contrast to the stable microbiome observed in adults, the infant microbiome is highly dynamic and associated with early life changes in the composition of bacteria, viruses and bacteriophages with age.

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Figure 1: Study design and metagenomic analysis of the infant gut virome.
Figure 2: Analysis of virome beta diversity.
Figure 3: Alterations in the eukaryotic RNA and DNA viruses with age and evidence of shared viromes between co-twins.
Figure 4: Decrease in bacteriophage richness and diversity with age coincides with a shift in bacteriophage composition.
Figure 5: Bacterial community expansion with age.
Figure 6: Inverse relationships between bacteriophages and bacteria.

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We thank the infants' families and physicians for their participation in, and cooperation with, the study. This work was supported in part by the Children's Discovery Institute (MD-FR-2013-292) and the US National Institutes of Health (5P30 DK052574 (Biobank, Digestive Diseases Research Core Centers) to P.I.T. and UH3AI083265 to P.I.T. and B.B.W.). P.I.T. and B.B.W. received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and from the Foundation for the National Institutes of Health (made possible by support from the Gerber Foundation). D.W. holds an Investigator in the Pathogenesis of Infectious Disease award from the Burroughs Wellcome Fund. E.S.L. is an Eli & Edythe Broad Fellow of the Life Sciences Research Foundation.

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E.S.L., L.R.H. and D.W. conceived and designed the experiments. L.D., I.K.B. and E.S.L. prepared samples for sequencing. E.S.L and I.K.B. performed PCR experiments. E.S.L., G.Z. and Y.Z. processed and analyzed the sequencing data. P.I.T., B.B.W. and I.M.N. recruited the study participants and managed the metadata. E.S.L., L.R.H., D.W. and P.I.T. wrote and edited the manuscript.

Correspondence to David Wang or Lori R Holtz.

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Lim, E., Zhou, Y., Zhao, G. et al. Early life dynamics of the human gut virome and bacterial microbiome in infants. Nat Med 21, 1228–1234 (2015). https://doi.org/10.1038/nm.3950

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