Expanding known viral diversity in the healthy infant gut

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  • Shiraz A. Shah
  • Anders G. Pedersen
  • Moïra B. Dion
  • Josué L. Castro-Mejía
  • Ronalds Silins
  • Fie O. Romme
  • Romain Sausset
  • Leon E. Jessen
  • Eric Olo Ndela
  • Mathis Hjelmsø
  • Tamsin A. Redgwell
  • Cristina Leal Rodríguez
  • Gisle Vestergaard
  • Hans Bisgaard
  • Francois Enault
  • Sylvain Moineau
  • Marie Agnès Petit

The gut microbiome is shaped through infancy and impacts the maturation of the immune system, thus protecting against chronic disease later in life. Phages, or viruses that infect bacteria, modulate bacterial growth by lysis and lysogeny, with the latter being especially prominent in the infant gut. Viral metagenomes (viromes) are difficult to analyse because they span uncharted viral diversity, lacking marker genes and standardized detection methods. Here we systematically resolved the viral diversity in faecal viromes from 647 1-year-olds belonging to Copenhagen Prospective Studies on Asthma in Childhood 2010, an unselected Danish cohort of healthy mother–child pairs. By assembly and curation we uncovered 10,000 viral species from 248 virus family-level clades (VFCs). Most (232 VFCs) were previously unknown, belonging to the Caudoviricetes viral class. Hosts were determined for 79% of phage using clustered regularly interspaced short palindromic repeat spacers within bacterial metagenomes from the same children. Typical Bacteroides-infecting crAssphages were outnumbered by undescribed phage families infecting Clostridiales and Bifidobacterium. Phage lifestyles were conserved at the viral family level, with 33 virulent and 118 temperate phage families. Virulent phages were more abundant, while temperate ones were more prevalent and diverse. Together, the viral families found in this study expand existing phage taxonomy and provide a resource aiding future infant gut virome research.

TidsskriftNature Microbiology
Sider (fra-til)986–998
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We express our deepest gratitude to the children and families of the COPSAC2010 cohort study for all their support and commitment. We acknowledge and appreciate the unique efforts of the COPSAC research team. This work is supported by the Joint Programming Initiative ‘Healthy Diet for a Healthy Life’, specifically here, the Danish Agency for Science and Higher Education, Institut National de la Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and the Canadian Institutes of Health Research (Team grant on Intestinal Microbiomics, Institute of Nutrition, Metabolism, and Diabetes, grant number 143924). M.B.D. is recipient of graduate scholarships from the Fonds de Recherche du Québec—Nature et Technologies (259257) as well as Sentinel North and is a recipient of the Goran-Enhorning Graduate Student Research Award from the Canadian Allergy, Asthma and Immunology Foundation. J.T. is supported by the BRIDGE Translational Excellence Program (bridge.ku.dk) at the Faculty of Health and Medical Sciences, University of Copenhagen, funded by the Novo Nordisk Foundation (grant no. NNF18SA0034956). S.M. holds the Tier 1 Canada Research Chair in Bacteriophages (950-232136). S.A.S. is a recipient of a Novo Nordisk Foundation project grant in basic bioscience (NNF18OC0052965), along with M.A.R., J.S. and D.S.N. are recipients of Novo Nordisk Foundation grant NNF20OC0061029.

Publisher Copyright:
© 2023, The Author(s).

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