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Viral biogeography of the mammalian gut and parenchymal organs

Nature Microbiology volume 7, pages 1301–1311 (2022)Cite this article

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Abstract

The mammalian virome has been linked to health and disease but our understanding of how it is structured along the longitudinal axis of the mammalian gastrointestinal tract (GIT) and other organs is limited. Here, we report a metagenomic analysis of the prokaryotic and eukaryotic virome occupying luminal and mucosa-associated habitats along the GIT, as well as parenchymal organs (liver, lung and spleen), in two representative mammalian species, the domestic pig and rhesus macaque (six animals per species). Luminal samples from the large intestine of both mammals harboured the highest loads and diversity of bacteriophages (class Caudoviricetes, family Microviridae and others). Mucosal samples contained much lower viral loads but a higher proportion of eukaryotic viruses (families Astroviridae, Caliciviridae, Parvoviridae). Parenchymal organs contained bacteriophages of gut origin, in addition to some eukaryotic viruses. Overall, GIT virome composition was specific to anatomical region and host species. Upper GIT and mucosa-specific viruses were greatly under-represented in distal colon samples (a proxy for faeces). Nonetheless, certain viral and phage species were ubiquitous in all samples from the oral cavity to the distal colon. The dataset and its accompanying methodology may provide an important resource for future work investigating the biogeography of the mammalian gut virome.

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Fig. 1: Abundance of different viral families along the GIT and in parenchymal organs of domestic pigs and rhesus macaques.
Fig. 2: α- and β-diversity of viromes in various anatomical sites in domestic pigs (n = 6) and rhesus macaques (n = 6).
Fig. 3: Sharing of viral genomic contigs between different anatomical sites in pigs (n = 6).
Fig. 4: Sharing of viral genomic contigs between different anatomical sites in macaques (n = 6).

Data availability

All data needed to evaluate the conclusions in the paper are present in the paper, Supplementary Information file and the additional dataset available at https://doi.org/10.6084/m9.figshare.15149247.v2. Raw sequencing data are available from NCBI databases under BioProject PRJNA753514. Source data are provided with this paper.

Code availability

Source data and custom R code used in this study are available at https://doi.org/10.6084/m9.figshare.15149247.v2. Further information and requests for data, code and resources should be directed to and will be fulfilled by A. Shkoporov and C. Hill.

Change history

  • 14 September 2022

    In the version of this article initially published, color overlays in Fig. 3b were missing or incorrect. The image has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

This research was conducted with the financial support of Science Foundation Ireland (SFI) under grant number SFI/12/RC/2273 (C. Hill and R.P.R.), an SFI's Spokes Programme which is co-funded under the European Regional Development Fund under grant number SFI/14/SP APC/B3032, Wellcome Trust Research Career Development Fellowship (220646/Z/20/Z0) (A.N.S.); and a research grant from Janssen Biotech, Inc. (C. Hill and R.P.R.). This research was funded in whole, or in part, by the Wellcome Trust (220646/Z/20/Z). For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. We thank T. Haaksma (BPRC) for his technical help with animal sampling, as well as J. Fitzgerald and J. Eckenberger for the fruitful discussion of statistical methods used in the study. The schematics in Figs. 1–4 were created with BioRender.com.

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Author notes

  1. These authors contributed equally: Andrey N. Shkoporov, Stephen R. Stockdale.

Authors and Affiliations

  1. APC Microbiome Ireland, University College Cork, Cork, Ireland

    Andrey N. Shkoporov, Stephen R. Stockdale, Aonghus Lavelle, Cara Heuston, Aditya Upadrasta, Ekaterina V. Khokhlova, Imme van der Kamp, Lorraine A. Draper, R. Paul Ross & Colin Hill

  2. School of Microbiology, University College Cork, Cork, Ireland

    Andrey N. Shkoporov, R. Paul Ross & Colin Hill

  3. Biomedical Primate Research Centre, Rijswijk, the Netherlands

    Ivanela Kondova, Boudewijn Ouwerling & Jan A. M. Langermans

  4. Department of Population Health Sciences, Utrecht University, Utrecht, the Netherlands

    Jan A. M. Langermans

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Contributions

A.N.S., S.R.S., R.P.R. and C. Hill conceived the study. A.N.S., S.R.S., A.L., I.K., L.A.D., C. Heuston and J.A.M.L. designed the study. A.N.S., S.R.S., A.L., I.K., C. Heuston, A.U., E.V.K., I.v.d.K. and B.O. undertook data acquisition. A.N.S., S.R.S., A.L., I.K., C. Heuston, J.A.M.L., L.A.D., R.P.R. and C. Hill analysed and interpreted the results. A.N.S. was responsible for the software. All authors contributed to drafting and revising of the manuscript.

Corresponding authors

Correspondence to Andrey N. Shkoporov or Colin Hill.

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Nature Microbiology thanks Laurent Debarbieux, Guanxiang Liang, Corinne Maurice and Alejandro Reyes for their contribution to the peer review of this work. Peer reviewer reports are available.

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Extended data

Extended Data Fig. 1 Catalogue of viral genomic contigs assembled from trimmed and filtered Illumina reads (n = 107,680).

a, Average read coverage vs. contig length, categories of viral genomic contigs identified by CheckV (high-quality genomes vs genome fragments according to definitions given by the MIUViG standard); b, distribution of viral genomic contigs by completeness level as predicted by CheckV with high quality draft and complete genomes by MIUViG standard highlighted in blue; c, cumulative fractional abundance of genomic contigs with different levels of completeness.

Source data

Extended Data Fig. 2 Taxonomic distribution, size, and completeness of viral genomic contigs.

Different viral families are shown in separate panels. Assignments are based on Demovir script. Contig size is plotted on log10-scaled x-axis. Contig completeness is predicted using CheckV.

Source data

Extended Data Fig. 3 Aggregated fractional abundance of viral families across all anatomical sites in pigs (n = 6) and macaques (n = 6) in the study.

Rows represent viral families, columns – sites in individual animals; the top annotation bar represent tissue types (lumen vs mucosa). Data is log10-transformed and presented with hierarchical clustering based on relative abundance patterns.

Source data

Extended Data Fig. 4 Sharing of viral genomic contigs between different anatomical sites in individual pigs (n = 6).

Vertical grey rectangles height is proportional to viral richness (individual genomic contig counts) at each location, aggregated across luminal and mucosal samples; thickness of coloured connectors is proportional with the number of genomic contigs of each viral family shared between pairs of locations; SI, small intestine; LI, large intestine; Prox/Mid/Dist, proximal, medial and distal portions, respectively; unclassified genomic contigs were excluded; C, fraction of viral contig diversity from each organ represented in the distal LI.

Source data

Extended Data Fig. 5 Sharing of viral genomic contigs between different anatomical sites in individual macaques (n = 6).

Vertical grey rectangles height is proportional to viral richness (individual genomic contig counts) at each location, aggregated across luminal and mucosal samples; thickness of coloured connectors is proportional with the number of genomic contigs of each viral family shared between pairs of locations; SI, small intestine; LI, large intestine; Prox/Mid/Dist, proximal, medial and distal portions, respectively; unclassified genomic contigs were excluded; C, fraction of viral contig diversity from each organ represented in the distal LI.

Source data

Extended Data Fig. 6 Numbers of viral genomic contigs shared between pairs of organs in pigs and macaques.

Numbers of shared contigs are expressed as aggregate counts of unique contigs shared between sites across all animals for each of the two species; SI, small intestine; LI, large intestine; Prox/Mid/Dist, proximal, medial and distal portions, respectively.

Source data

Extended Data Fig. 7 Absolute counts of some of the most ubiquitous viral genomic contigs present in pigs and macaques.

Only contigs with >50% estimated completeness and shared between 6 or more sites in any of the animals are displayed. Each line corresponds to an individual genomic contig (potentially collapsing multiple viral strains). Colours are according to viral families. Each panel represent an individual animal.

Source data

Supplementary information

Supplementary Information

Supplementary Methods and Results and Figs. 1–13.

Reporting Summary.

Peer Review File.

Supplementary Table 1

Sample metadata table.

Source data

Source Data Fig. 1

Absolute viral counts per anatomical site, per animal.

Source Data Fig. 2

Ordination plot, coordinates. Alpha diversity values, per sample. Heat map, matrix.

Source Data Fig. 3

Fraction of diversity shared from one site to another. Number of contigs of each family shared between sites. Fraction of diversity represented in the distal colon.

Source Data Fig. 4

Fraction of diversity shared from one site to another. Number of contigs of each family shared between sites. Fraction of diversity represented in the distal colon.

Source Data Extended Data Fig. 1

Viral contigs: size, cumulative abundance, completeness estimate.

Source Data Extended Data Fig. 2

Viral contigs: size and completeness grouped by viral family.

Source Data Extended Data Fig. 3

Log-transformed fractional abundance of viral families across samples.

Source Data Extended Data Fig. 4

Number of contigs of each family shared between sites, per animal.

Source Data Extended Data Fig. 5

Number of contigs of each family shared between sites, per animal.

Source Data Extended Data Fig. 6

List of contigs shared between pairs of anatomical sites, per viral family, per animal species.

Source Data Extended Data Fig. 7

Absolute viral counts for the most ubiquitous viral contigs, per viral family, per animal.

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Shkoporov, A.N., Stockdale, S.R., Lavelle, A. et al. Viral biogeography of the mammalian gut and parenchymal organs. Nat Microbiol 7, 1301–1311 (2022). https://doi.org/10.1038/s41564-022-01178-w

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