The infant gut virome is associated with preschool asthma risk independently of bacteria

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Cristina Leal Rodríguez
Shiraz A. Shah
Rasmussen, Morten Arendt
Jonathan Thorsen
Ulrika Boulund
Casper-Emil Tingskov Pedersen
Josué L. Castro-Mejía
Poulsen, Christina Egeø
Casper Sahl Poulsen
Deng, Ling
Larsen, Frej Andreas Nøhr
Widdowson, Michael Lawrence
Zhang, Yichang
Sørensen, Søren Johannes
Sylvain Moineau
Marie Agnès Petit
Chawes, Bo Lund Krogsgaard
Bønnelykke, Klaus
Nielsen, Dennis Sandris
Stokholm, Jakob

Bacteriophage (also known as phage) communities that inhabit the gut have a major effect on the structure and functioning of bacterial populations, but their roles and association with health and disease in early life remain unknown. Here, we analyze the gut virome of 647 children aged 1 year from the Copenhagen Prospective Studies on Asthma in Childhood₂₀₁₀ (COPSAC₂₀₁₀) mother–child cohort, all deeply phenotyped from birth and with longitudinally assessed asthma diagnoses. Specific temperate gut phage taxa were found to be associated with later development of asthma. In particular, the joint abundances of 19 caudoviral families were found to significantly contribute to this association. Combining the asthma-associated virome and bacteriome signatures had additive effects on asthma risk, implying an independent virome–asthma association. Moreover, the virome-associated asthma risk was modulated by the host TLR9 rs187084 gene variant, suggesting a direct interaction between phages and the host immune system. Further studies will elucidate whether phages, alongside bacteria and host genetics, can be used as preclinical biomarkers for asthma.

Originalsprog	Engelsk
Tidsskrift	Nature Medicine
Vol/bind	30
Sider (fra-til)	138-148
Antal sider	11
ISSN	1078-8956
DOI	https://doi.org/10.1038/s41591-023-02685-x
Status	Udgivet - 2023

Bibliografisk note

Funding Information:
All funding received by COPSAC is listed at https://copsac.com . The Lundbeck Foundation (R16-A1694), the Ministry of Health (903516), the Danish Council for Strategic Research (0603-00280B) and the Capital Region Research Foundation have provided core support to the COPSAC research center. 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 in Intestinal Microbiomics, Institute of Nutrition, Metabolism, and Diabetes, 143924). S.A.S. and M.A.R. are recipients of a Novo Nordisk Foundation project grant in basic bioscience (grant NNF18OC0052965). J.S. and D.S.N. are recipients of Novo Nordisk Foundation grant NNF20OC0061029. J.S. received funding from the Danish Council for Independent Research (8045-00081B). J.T. is supported by the BRIDGE Translational Excellence Program at the Faculty of Health and Medical Sciences, University of Copenhagen, funded by the Novo Nordisk Foundation (grant NNF18SA0034956). C.-E.T.P. is funded by the Lundbeck Foundation (grant R322-2019-2735). S.M. holds the Canada Research Chair in Bacteriophages. Y.Z. is recipient of a PhD scholarship from the Chinese Scholarship Council (CSC). B.C. is funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 946228).

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.

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