Distinct gut microbiome ecology may be implicated in the prevention of aging-related diseases as it influences systemic immune function and resistance to infections. Yet, the viral component of the microbiome throughout different stages in life remains unexplored. Here we present a characterization of the centenarian gut virome using previously published metagenomes from 195 individuals from Japan and Sardinia. Compared with gut viromes of younger adults (>18 yr) and older individuals (>60 yr), centenarians had a more diverse virome including previously undescribed viral genera, such as viruses associated with Clostridia. A population shift towards higher lytic activity was also observed. Finally, we investigated phage-encoded auxiliary functions that influence bacterial physiology, which revealed an enrichment of genes supporting key steps in sulfate metabolic pathways. Phage and bacterial members of the centenarian microbiome displayed an increased potential for converting methionine to homocysteine, sulfate to sulfide and taurine to sulfide. A greater metabolic output of microbial hydrogen sulfide in centenarians may in turn support mucosal integrity and resistance to pathobionts.
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This paper analyses existing, publicly available data. The raw sequencing files used in this study for Centenarian, Sardinian, Tanzanian 300FG and EDIA microbiome datasets are available at the NCBI database under accession numbers PRJNA675598, PRJEB25514, PRJNA686265 and PRJNA707065, respectively. The viral genomes used to establish previously undescribed viral biodiversity are available from the Metagenomic Viruses Database (https://portal.nersc.gov/MGV). Additional files including vOTU genomes, phylogenetic tree, VOG marker table and master annotation table for vOTUs can be accessed at Zenodo (https://doi.org/10.5281/zenodo.6579480). Source data are provided in Supplementary Information.
All original code has been deposited at GitHub and is publicly available as of the date of publication. Workflows and supporting code can be accessed at the following repository: https://github.com/RasmussenLab/vCentenarian. Any additional information required to reanalyse the data reported in this paper is available from the lead contact (D.R.P.) upon request.
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We thank E. Heppenheimer for editorial assistance during text and figure preparation.
The study was funded in part by the Novo Nordisk Foundation (NNF21SA0072102); the Center for Microbiome Informatics and Therapeutics (R.J.X.); NIH grant DK043351 (R.J.X.); and NIH grant DK120485 (R.J.X.). J.J. and S.R. were supported by the Novo Nordisk Foundation (grant NNF14CC0001). K.H., K.A. and Y.A. were supported by Moonshot Research and Development Program (JP22zf0127007) and NeDDTrim (JP21ae0121041) from AMED Japan. K.H. and K.A. were supported by MEXT Japan World Premier International Research Center Initiative (WPI). The EDIA study was supported by NIH grant 1DP3DK094338-01 (M.K.) and by the Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research No. 250114 (M.K.).
R.J.X. is a co-founder of Celsius Therapeutics and Jnana Therapeutics, a member of the Scientific Advisory Board of Nestle, and a member of the Board of Directors at Moonlake Immunotherapeutics. These organizations had no role in supporting this study. The other authors declare no competing interests.
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Supplementary Figs. 1–5.
Table 1. vOTU genus counts (known and new) with number of vOTUs in each. Bacterial host annotation at each taxonomic lineage level. Table 2. Integrated prophage summary table of prophages identified in bacterial isolates of centenarians. Contains isolate ID, length and integration coordinates. Table 3. Test statistics for viral bacterial abundance ratios between age groups of prevalent sulfate genes. Table 4. Test statistics for dissimilatory sulfate microbiome abundance between age groups. Table 5. CE91 isolates information including taxonomy and genome quality.
MSP MAG taxonomy.
Virus host annotation.
Virus master table.
Figures 2 and 3 viral abundance matrix.
Figures 3 and 4 MSP (bacterial) abundance matrix.
Figure 4 viral to bacterial ratios between bacteria and species at host level.
Figures 5 and 6 auxiliary metabolic gene measurements.
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Johansen, J., Atarashi, K., Arai, Y. et al. Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan. Nat Microbiol 8, 1064–1078 (2023). https://doi.org/10.1038/s41564-023-01370-6