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


Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
15 Dec 2023
Historique:
received: 14 06 2023
accepted: 07 11 2023
medline: 16 12 2023
pubmed: 16 12 2023
entrez: 15 12 2023
Statut: aheadofprint

Résumé

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 Childhood

Identifiants

pubmed: 38102298
doi: 10.1038/s41591-023-02685-x
pii: 10.1038/s41591-023-02685-x
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF20OC0061029
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF18OC0052965
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF18SA0034956
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF20OC0061029
Organisme : Det Frie Forskningsråd (Danish Council for Independent Research)
ID : 8045-00081B
Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R322-2019-2735
Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R16-A1694
Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R16-A1694
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 946228
Organisme : Strategiske Forskningsråd (Danish Council for Strategic Research)
ID : 0603-00280B
Organisme : Strategiske Forskningsråd (Danish Council for Strategic Research)
ID : 0603-00280B

Informations de copyright

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

Références

Bisgaard, H. & Szefler, S. Prevalence of asthma-like symptoms in young children. Pediatr. Pulmon. 42, 723–728 (2007).
doi: 10.1002/ppul.20644
Holgate, S. T. The epidemic of allergy and asthma. Nature 402, 2–4 (1999).
doi: 10.1038/35037000
Gensollen, T., Iyer, S. S., Kasper, D. L. & Blumberg, R. S. How colonization by microbiota in early life shapes the immune system. Science 352, 539–544 (2016).
pubmed: 27126036 pmcid: 5050524 doi: 10.1126/science.aad9378
Vatanen, T. et al. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell 165, 1551 (2016).
pubmed: 27259157 doi: 10.1016/j.cell.2016.05.056
Depner, M. et al. Maturation of the gut microbiome during the first year of life contributes to the protective farm effect on childhood asthma. Nat. Med. 26, 1766–1775 (2020).
pubmed: 33139948 doi: 10.1038/s41591-020-1095-x
Stokholm, J. et al. Maturation of the gut microbiome and risk of asthma in childhood. Nat. Commun. 9, 141 (2018).
pubmed: 29321519 pmcid: 5762761 doi: 10.1038/s41467-017-02573-2
Bisgaard, H. et al. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J. Allergy Clin. Immunol. 128, 646–52.e1–5 (2011).
pubmed: 21782228 doi: 10.1016/j.jaci.2011.04.060
Penders, J. et al. Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut 56, 661–667 (2007).
pubmed: 17047098 doi: 10.1136/gut.2006.100164
Vijay, A. & Valdes, A. M. Role of the gut microbiome in chronic diseases: a narrative review. Eur. J. Clin. Nutr. 76, 489–501 (2022).
pubmed: 34584224 doi: 10.1038/s41430-021-00991-6
Shkoporov, A. N. & Hill, C. Bacteriophages of the human gut: the ‘known unknown’ of the microbiome. Cell Host Microbe 25, 195–209 (2019).
pubmed: 30763534 doi: 10.1016/j.chom.2019.01.017
Sausset, R., Petit, M. A., Gaboriau-Routhiau, V. & De Paepe, M. New insights into intestinal phages. Mucosal Immunol. 13, 205–215 (2020).
pubmed: 31907364 pmcid: 7039812 doi: 10.1038/s41385-019-0250-5
Liang, G. & Bushman, F. D. The human virome: assembly, composition and host interactions. Nat. Rev. Microbiol. 19, 514–527 (2021).
pubmed: 33785903 pmcid: 8008777 doi: 10.1038/s41579-021-00536-5
Duerkop, B. A. et al. A composite bacteriophage alters colonization by an intestinal commensal bacterium. Proc. Natl Acad. Sci. USA 109, 17621–17626 (2012).
pubmed: 23045666 pmcid: 3491505 doi: 10.1073/pnas.1206136109
Barr, J. J. et al. Bacteriophage adhering to mucus provide a non–host-derived immunity. Proc. Natl Acad. Sci. 110, 10771–10776 (2013).
pubmed: 23690590 pmcid: 3696810 doi: 10.1073/pnas.1305923110
Van Belleghem, J. D., Dąbrowska, K., Vaneechoutte, M., Barr, J. J. & Bollyky, P. L. Interactions between bacteriophage, bacteria, and the mammalian immune system. Viruses 11, 10 (2018).
pubmed: 30585199 pmcid: 6356784 doi: 10.3390/v11010010
Sweere, J. M. et al. Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection. Science 363, eaat9691 (2019).
pubmed: 30923196 pmcid: 6656896 doi: 10.1126/science.aat9691
Focà, A. et al. Gut inflammation and immunity: what is the role of the human gut virome? Mediat. Inflamm. 2015, 326032 (2015).
doi: 10.1155/2015/326032
Bisgaard, H. et al. Deep phenotyping of the unselected COPSAC2010 birth cohort study. Clin. Exp. Allergy 43, 1384–1394 (2013).
pubmed: 24118234 pmcid: 4158856 doi: 10.1111/cea.12213
Shah, S. A. et al. Expanding known viral diversity in the healthy infant gut. Nat. Microbiol. 8, 986–998 (2023).
pubmed: 37037943 pmcid: 10159846 doi: 10.1038/s41564-023-01345-7
Manrique, P. et al. Healthy human gut phageome. Proc. Natl Acad. Sci. USA 113, 10400–10405 (2016).
pubmed: 27573828 pmcid: 5027468 doi: 10.1073/pnas.1601060113
Zhang, Y. et al. The influence of early life exposures on the infant gut virome. Preprint at https://www.biorxiv.org/content/10.1101/2023.03.05.531203v1 (2023)
Górski, A. et al. Bacteriophage translocation. FEMS Immunol. Med. Microbiol. 46, 313–319 (2006).
pubmed: 16553803 doi: 10.1111/j.1574-695X.2006.00044.x
Bichet, M. C. et al. Bacteriophage uptake by mammalian cell layers represents a potential sink that may impact phage therapy. iScience 24, 102287 (2021).
pubmed: 33855278 pmcid: 8024918 doi: 10.1016/j.isci.2021.102287
Shkoporov, A. N. et al. Viral biogeography of the mammalian gut and parenchymal organs. Nat. Microbiol. 7, 1301–1311 (2022).
pubmed: 35918425 pmcid: 7614033 doi: 10.1038/s41564-022-01178-w
Kumagai, Y., Takeuchi, O. & Akira, S. TLR9 as a key receptor for the recognition of DNA. Adv. Drug Deliv. Rev. 60, 795–804 (2008).
pubmed: 18262306 doi: 10.1016/j.addr.2007.12.004
Wagner, H. The immunobiology of the TLR9 subfamily. Trends Immunol. 25, 381–386 (2004).
pubmed: 15207506 doi: 10.1016/j.it.2004.04.011
Wagner, H. Interactions between bacterial CpG-DNA and TLR9 bridge innate and adaptive immunity. Curr. Opin. Microbiol. 5, 62–69 (2002).
pubmed: 11834371 doi: 10.1016/S1369-5274(02)00287-4
Hochrein, H. et al. Herpes simplex virus type-1 induces IFN-α production via Toll-like receptor 9-dependent and -independent pathways. Proc. Natl Acad. Sci. 101, 11416–11421 (2004).
pubmed: 15272082 pmcid: 509215 doi: 10.1073/pnas.0403555101
Gogokhia, L. et al. Expansion of bacteriophages is linked to aggravated intestinal inflammation and colitis. Cell Host Microbe 25, 285–299.e8 (2019).
pubmed: 30763538 pmcid: 6885004 doi: 10.1016/j.chom.2019.01.008
Susi, M. D. et al. Toll-like receptor 9 polymorphisms and Helicobacter pylori influence gene expression and risk of gastric carcinogenesis in the Brazilian population. World J. Gastrointest. Oncol. 11, 998–1010 (2019).
pubmed: 31798780 pmcid: 6883180 doi: 10.4251/wjgo.v11.i11.998
Chen, X. et al. A genetic variant in the promoter region of Toll-like receptor 9 and cervical cancer susceptibility. DNA Cell Biol. 31, 766–771 (2012).
pubmed: 22059466 doi: 10.1089/dna.2011.1427
Tao, K. et al. Genetic variations of Toll-like receptor 9 predispose to systemic lupus erythematosus in Japanese population. Ann. Rheum. Dis. 66, 905–909 (2007).
pubmed: 17344245 pmcid: 1955115 doi: 10.1136/ard.2006.065961
Leoratti, F. M. S. et al. Variants in the toll-like receptor signaling pathway and clinical outcomes of malaria. J. Infect. Dis. 198, 772–780 (2008).
pubmed: 18662133 doi: 10.1086/590440
Bank, S. et al. Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort. PLoS ONE 9, e98815 (2014).
pubmed: 24971461 pmcid: 4074037 doi: 10.1371/journal.pone.0098815
Kormann, M. S. D. et al. Toll-like receptor heterodimer variants protect from childhood asthma. J. Allergy Clin. Immunol. 122, 86–92, 92.e1–8 (2008).
pubmed: 18547625 doi: 10.1016/j.jaci.2008.04.039
Genuneit, J. et al. A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2. Clin. Exp. Allergy 39, 1875–1888 (2009).
pubmed: 20085599 doi: 10.1111/j.1365-2222.2009.03364.x
Nuolivirta, K. et al. Post-bronchiolitis wheezing is associated with toll-like receptor 9 rs187084 gene polymorphism. Sci. Rep. 6, 31165 (2016).
pubmed: 27498757 pmcid: 4976338 doi: 10.1038/srep31165
Norman, J. M. et al. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160, 447–460 (2015).
pubmed: 25619688 pmcid: 4312520 doi: 10.1016/j.cell.2015.01.002
Clooney, A. G. et al. Whole-virome analysis sheds light on viral dark matter in inflammatory bowel disease. Cell Host Microbe 26, 764–778.e5 (2019).
pubmed: 31757768 doi: 10.1016/j.chom.2019.10.009
Yang, K. et al. Alterations in the gut virome in obesity and type 2 diabetes mellitus. Gastroenterology 161, 1257–1269.e13 (2021).
pubmed: 34175280 doi: 10.1053/j.gastro.2021.06.056
Jiang, L. et al. Intestinal virome in patients with alcoholic hepatitis. Hepatology 72, 2182–2196 (2020).
pubmed: 32654263 doi: 10.1002/hep.31459
Johnson, C. H. et al. Metabolism links bacterial biofilms and colon carcinogenesis. Cell Metab. 21, 891–897 (2015).
pubmed: 25959674 pmcid: 4456201 doi: 10.1016/j.cmet.2015.04.011
Khan Mirzaei, M. et al. Bacteriophages isolated from stunted children can regulate gut bacterial communities in an age-specific manner. Cell Host Microbe 27, 199–212.e5 (2020).
pubmed: 32053789 pmcid: 7013830 doi: 10.1016/j.chom.2020.01.004
Tisza, M. J. & Buck, C. B. A catalog of tens of thousands of viruses from human metagenomes reveals hidden associations with chronic diseases. Proc. Natl Acad. Sci. USA 118, e2023202118 (2021).
pubmed: 34083435 pmcid: 8201803 doi: 10.1073/pnas.2023202118
Zhao, G. et al. Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children. Proc. Natl Acad. Sci. USA 114, E6166–E6175 (2017).
pubmed: 28696303 pmcid: 5544325 doi: 10.1073/pnas.1706359114
Megremis, S. et al. Respiratory eukaryotic virome expansion and bacteriophage deficiency characterize childhood asthma. Sci. Rep. 13, 8319 (2023).
pubmed: 37221274 pmcid: 10205716 doi: 10.1038/s41598-023-34730-7
Choi, S. et al. Lung virome: new potential biomarkers for asthma severity and exacerbation. J. Allergy Clin. Immunol. 148, 1007–1015.e9 (2021).
pubmed: 33757721 doi: 10.1016/j.jaci.2021.03.017
Olo Ndela, E. et al. Reekeekee- and roodoodooviruses, two different clades constituted by the smallest DNA phages. Virus Evol. 9, veac123 (2023).
pubmed: 36694818 doi: 10.1093/ve/veac123
Shkoporov, A. N. et al. The human gut virome is highly diverse, stable, and individual specific. Cell Host Microbe 26, 527–541.e5 (2019).
pubmed: 31600503 doi: 10.1016/j.chom.2019.09.009
Zuo, T. et al. Human-gut-DNA virome variations across geography, ethnicity, and urbanization. Cell Host Microbe 28, 741–751.e4 (2020).
pubmed: 32910902 doi: 10.1016/j.chom.2020.08.005
Lim, E. S. et al. Early life dynamics of the human gut virome and bacterial microbiome in infants. Nat. Med. 21, 1228–1234 (2015).
pubmed: 26366711 pmcid: 4710368 doi: 10.1038/nm.3950
Liang, G. et al. The stepwise assembly of the neonatal virome is modulated by breastfeeding. Nature 581, 470–474 (2020).
pubmed: 32461640 pmcid: 7263352 doi: 10.1038/s41586-020-2192-1
Vicente, C. T., Revez, J. A. & Ferreira, M. A. R. Lessons from ten years of genome-wide association studies of asthma. Clin. Transl. Immunol. 6, e165 (2017).
doi: 10.1038/cti.2017.54
Spycher, B. D. et al. Genome-wide prediction of childhood asthma and related phenotypes in a longitudinal birth cohort. J. Allergy Clin. Immunol. 130, 503–9.e7 (2012).
pubmed: 22846752 pmcid: 4871225 doi: 10.1016/j.jaci.2012.06.002
Bushman, F. & Liang, G. Assembly of the virome in newborn human infants. Curr. Opin. Virol. 48, 17–22 (2021).
pubmed: 33813257 pmcid: 8187319 doi: 10.1016/j.coviro.2021.03.004
Neil, J. A. & Cadwell, K. The intestinal virome and immunity. J. Immunol. 201, 1615–1624 (2018).
pubmed: 30181300 doi: 10.4049/jimmunol.1800631
Adiliaghdam, F. et al. Human enteric viruses autonomously shape inflammatory bowel disease phenotype through divergent innate immunomodulation. Sci. Immunol. 7, eabn6660 (2022).
pubmed: 35394816 pmcid: 9416881 doi: 10.1126/sciimmunol.abn6660
Lester, S. N. & Li, K. Toll-like receptors in antiviral innate immunity. J. Mol. Biol. 426, 1246–1264 (2014).
pubmed: 24316048 doi: 10.1016/j.jmb.2013.11.024
Rifkin, I. R., Leadbetter, E. A., Busconi, L., Viglianti, G. & Marshak-Rothstein, A. Toll-like receptors, endogenous ligands, and systemic autoimmune disease. Immunol. Rev. 204, 27–42 (2005).
pubmed: 15790348 doi: 10.1111/j.0105-2896.2005.00239.x
Marshak-Rothstein, A. Toll-like receptors in systemic autoimmune disease. Nat. Rev. Immunol. 6, 823–835 (2006).
pubmed: 17063184 pmcid: 7097510 doi: 10.1038/nri1957
Fischer, J. et al. Sex-specific effects of TLR9 promoter variants on spontaneous clearance of HCV infection. Gut 66, 1829–1837 (2017).
pubmed: 27196570 doi: 10.1136/gutjnl-2015-310239
Almqvist, C., Ekberg, S., Rhedin, S. & Fang, F. Season of birth, childhood asthma and allergy in a nationwide cohort–Mediation through lower respiratory infections. Clin. Exp. Allergy 50, 222–230 (2020).
pubmed: 31782836 doi: 10.1111/cea.13542
Schoos, A.-M. M. et al. Season of birth impacts the neonatal nasopharyngeal microbiota. Children 7, 45 (2020).
pubmed: 32403236 pmcid: 7278723 doi: 10.3390/children7050045
Thorsen, J. et al. Infant airway microbiota and topical immune perturbations in the origins of childhood asthma. Nat. Commun. 10, 5001 (2019).
pubmed: 31676759 pmcid: 6825176 doi: 10.1038/s41467-019-12989-7
Strachan, D. P. Hay fever, hygiene, and household size. BMJ Brit. Med. J. 299, 1259–1260 (1989).
pubmed: 2513902 doi: 10.1136/bmj.299.6710.1259
Rook, G. A. W. & Brunet, L. R. Microbes, immunoregulation, and the gut. Gut 54, 317–320 (2005).
pubmed: 15710972 pmcid: 1774411 doi: 10.1136/gut.2004.053785
Christensen, E. D. et al. The developing airway and gut microbiota in early life is influenced by age of older siblings. Microbiome 10, 106 (2022).
pubmed: 35831879 pmcid: 9277889 doi: 10.1186/s40168-022-01305-z
Bertolini, V. et al. Temporal variability and effect of environmental variables on airborne bacterial communities in an urban area of Northern Italy. Appl. Microbiol. Biotechnol. 97, 6561–6570 (2013).
pubmed: 23053100 doi: 10.1007/s00253-012-4450-0
Prussin, A. J. et al. Seasonal dynamics of DNA and RNA viral bioaerosol communities in a daycare center. Microbiome 7, 53 (2019).
pubmed: 30935423 pmcid: 6444849 doi: 10.1186/s40168-019-0672-z
Brum, J. R., Hurwitz, B. L., Schofield, O., Ducklow, H. W. & Sullivan, M. B. Seasonal dynamics of DNA and RNA viral bioaerosol communities in a daycare center. ISME J 10, 437–449 (2016).
pubmed: 26296067 doi: 10.1038/ismej.2015.125
Hevroni, G., Flores-Uribe, J., Béjà, O. & Philosof, A. Seasonal and diel patterns of abundance and activity of viruses in the Red Sea. Proc. Natl Acad. Sci. USA 117, 29738–29747 (2020).
pubmed: 33172994 pmcid: 7703586 doi: 10.1073/pnas.2010783117
Shkoporov, A. N., Turkington, C. J. & Hill, C. Mutualistic interplay between bacteriophages and bacteria in the human gut. Nat. Rev. Microbiol. https://doi.org/10.1038/s41579-022-00755-4 (2022).
doi: 10.1038/s41579-022-00755-4 pubmed: 35773472
Minot, S. et al. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res. 21, 1616–1625 (2011).
pubmed: 21880779 pmcid: 3202279 doi: 10.1101/gr.122705.111
Sutcliffe, S. G., Shamash, M., Hynes, A. P. & Maurice, C. F. Common oral medications lead to prophage induction in bacterial isolates from the human gut. Viruses 13, 455 (2021).
pubmed: 33799646 pmcid: 8000485 doi: 10.3390/v13030455
Heida, F. H. et al. Weight shapes the intestinal microbiome in preterm infants: results of a prospective observational study. BMC Microbiol. 21, 219 (2021).
pubmed: 34289818 pmcid: 8293572 doi: 10.1186/s12866-021-02279-y
Tun, H. M. et al. Exposure to household furry pets influences the gut microbiota of infants at 3–4 months following various birth scenarios. Microbiome 5, 1–14 (2017).
doi: 10.1186/s40168-017-0254-x
Bisgaard, H., Hermansen, M. N., Loland, L., Halkjaer, L. B. & Buchvald, F. Intermittent inhaled corticosteroids in infants with episodic wheezing. N. Engl. J. Med. 354, 1998–2005 (2006).
pubmed: 16687712 doi: 10.1056/NEJMoa054692
Bisgaard, H. et al. Fish oil-derived fatty acids in pregnancy and wheeze and asthma in offspring. N. Engl. J. Med. 375, 2530–2539 (2016).
pubmed: 28029926 doi: 10.1056/NEJMoa1503734
Deng, L. et al. A protocol for extraction of infective viromes suitable for metagenomics sequencing from low volume fecal samples. Viruses 11, e2023202118 (2019).
doi: 10.3390/v11070667
Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 17, 10 (2011).
doi: 10.14806/ej.17.1.200
Callahan, B. J. et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581–583 (2016).
pubmed: 27214047 pmcid: 4927377 doi: 10.1038/nmeth.3869
Bolyen, E. et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 37, 852–857 (2019).
pubmed: 31341288 pmcid: 7015180 doi: 10.1038/s41587-019-0209-9
Alishum, A. DADA2 formatted 16S rRNA gene sequences for both bacteria & archaea. Zenodo https://doi.org/10.5281/ZENODO.3188334 (2019)
R Core Team. R: a language and environment for statistical computing. The R Project for Statistical Computing https://www.R-project.org (2018).
McMurdie, P. J. & Holmes, S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE 8, e61217 (2013).
pubmed: 23630581 pmcid: 3632530 doi: 10.1371/journal.pone.0061217
Roux, S., Emerson, J. B., Eloe-Fadrosh, E. A. & Sullivan, M. B. Benchmarking viromics: an in silico evaluation of metagenome-enabled estimates of viral community composition and diversity. PeerJ 5, e3817 (2017).
pubmed: 28948103 pmcid: 5610896 doi: 10.7717/peerj.3817
Oksanen, J., Kindt, R., Legendre, P. & O’Hara, B. vegan: community ecology package. R package Version 2.4-3. https://CRAN.R-project.org/package=vegan (2017)
Tingley, D., Yamamoto, T., Hirose, K., Keele, L. & Imai, K. mediation: R package for causal mediation analysis. J. Stat. Softw. 59, 1–38 (2014).
doi: 10.18637/jss.v059.i05
Højsgaard, S., Halekoh, U. & Yan, J. The R Package geepack for Generalized Estimating Equations. J. Stat. Softw. 15, 1–11 (2006).

Auteurs

Cristina Leal Rodríguez (C)

Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark.

Shiraz A Shah (SA)

Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark.

Morten Arendt Rasmussen (MA)

Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark.
Department of Food Science, University of Copenhagen, Copenhagen, Denmark.

Jonathan Thorsen (J)

Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark.

Ulrika Boulund (U)

Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark.

Casper-Emil Tingskov Pedersen (CT)

Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark.
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Josué L Castro-Mejía (JL)

Department of Food Science, University of Copenhagen, Copenhagen, Denmark.

Christina Egeø Poulsen (CE)

Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark.

Casper Sahl Poulsen (CS)

Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark.

Ling Deng (L)

Department of Food Science, University of Copenhagen, Copenhagen, Denmark.

Frej Andreas Nøhr Larsen (FAN)

Department of Food Science, University of Copenhagen, Copenhagen, Denmark.

Michael Widdowson (M)

Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark.

Yichang Zhang (Y)

Department of Food Science, University of Copenhagen, Copenhagen, Denmark.

Søren J Sørensen (SJ)

Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Sylvain Moineau (S)

Département de Biochimie, de Microbiologie, et de Bio-Informatique, Faculté des Sciences et de Génie, Université Laval, Québec City, QC, Canada.
Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, Québec City, QC, Canada.
Félix d'Hérelle Reference Center for Bacterial Viruses, Université Laval, Québec City, QC, Canada.

Marie-Agnès Petit (MA)

Université Paris-Saclay, INRAE, Agroparistech, Micalis Institute, Jouy-en-Josas, France.

Bo Chawes (B)

Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark.

Klaus Bønnelykke (K)

Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark.

Dennis S Nielsen (DS)

Department of Food Science, University of Copenhagen, Copenhagen, Denmark.

Jakob Stokholm (J)

Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark. stokholm@copsac.com.
Department of Food Science, University of Copenhagen, Copenhagen, Denmark. stokholm@copsac.com.

Classifications MeSH