Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan

Joachim Johansen; Koji Atarashi; Yasumichi Arai; Nobuyoshi Hirose; Søren J Sørensen; Tommi Vatanen; Mikael Knip; Kenya Honda; Ramnik J Xavier; Simon Rasmussen; Damian R Plichta

doi:10.1038/s41564-023-01370-6

Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan

Nat Microbiol. 2023 Jun;8(6):1064-1078. doi: 10.1038/s41564-023-01370-6. Epub 2023 May 15.

Authors

Joachim Johansen^{1

2}, Koji Atarashi³, Yasumichi Arai⁴, Nobuyoshi Hirose⁴, Søren J Sørensen⁵, Tommi Vatanen^{1

6}, Mikael Knip^{6

7

8}, Kenya Honda³, Ramnik J Xavier⁹, Simon Rasmussen^{10

11}, Damian R Plichta¹²

Affiliations

¹ Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
² Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
³ Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
⁴ Center for Supercentenarian Medical Research, Keio University School of Medicine, Tokyo, Japan.
⁵ Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
⁶ Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁷ New Children's Hospital, Helsinki University Hospital, Helsinki, Finland.
⁸ Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.
⁹ Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA. [email protected].
¹⁰ Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [email protected].
¹¹ The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA. [email protected].
¹² Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA. [email protected].

PMID: 37188814
DOI: 10.1038/s41564-023-01370-6

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adult
Aged, 80 and over
Bacteriophages* / genetics
Centenarians
Humans
Longevity
Microbiota*
Virome
Viruses* / genetics

Grants and funding

DP3 DK094338/DK/NIDDK NIH HHS/United States