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Aberrant IgA responses to the gut microbiota during infancy precede asthma and allergy development

  • Majda Dzidic
    Affiliations
    Department of Clinical and Experimental Medicine, Unit of Autoimmunity and Immune Regulation, Linköping University, Linköping, Sweden

    Department of Health and Genomics, FISABIO Foundation, Center for Advanced Research in Public Health, Valencia, Spain

    Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Department of Biotechnology, Unit of Lactic Acid Bacteria and Probiotics, Valencia, Spain
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  • Thomas R. Abrahamsson
    Affiliations
    Department of Clinical and Experimental Medicine, Division of Paediatrics, Linköping University, Linköping, Sweden
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  • Alejandro Artacho
    Affiliations
    Department of Health and Genomics, FISABIO Foundation, Center for Advanced Research in Public Health, Valencia, Spain
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  • Bengt Björkstén
    Affiliations
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
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  • Maria Carmen Collado
    Affiliations
    Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Department of Biotechnology, Unit of Lactic Acid Bacteria and Probiotics, Valencia, Spain
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  • Author Footnotes
    ∗ These authors are senior authors and contributed equally to this work.
    Alex Mira
    Correspondence
    Alex Mira, PhD, Avenida de Cataluna 21, 46020 Valencia, Spain.
    Footnotes
    ∗ These authors are senior authors and contributed equally to this work.
    Affiliations
    Department of Health and Genomics, FISABIO Foundation, Center for Advanced Research in Public Health, Valencia, Spain
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  • Author Footnotes
    ∗ These authors are senior authors and contributed equally to this work.
    Maria C. Jenmalm
    Correspondence
    Corresponding author: Maria C. Jenmalm, PhD, Linköping University, Department of Clinical and Experimental Medicine, AIR/Clinical Immunology, 581 85 Linköping, Sweden.
    Footnotes
    ∗ These authors are senior authors and contributed equally to this work.
    Affiliations
    Department of Clinical and Experimental Medicine, Unit of Autoimmunity and Immune Regulation, Linköping University, Linköping, Sweden
    Search for articles by this author
  • Author Footnotes
    ∗ These authors are senior authors and contributed equally to this work.
Published:August 13, 2016DOI:https://doi.org/10.1016/j.jaci.2016.06.047

      Background

      Although a reduced gut microbiota diversity and low mucosal total IgA levels in infancy have been associated with allergy development, IgA responses to the gut microbiota have not yet been studied.

      Objective

      We sought to determine the proportions of IgA coating together with the characterization of the dominant bacteria, bound to IgA or not, in infant stool samples in relation to allergy development.

      Methods

      A combination of flow cytometric cell sorting and deep sequencing of the 16S rDNA gene was used to characterize the bacterial recognition patterns by IgA in stool samples collected at 1 and 12 months of age from children staying healthy or having allergic symptoms up to 7 years of age.

      Results

      The children with allergic manifestations, particularly asthma, during childhood had a lower proportion of IgA bound to fecal bacteria at 12 months of age compared with healthy children. These alterations cannot be attributed to differences in IgA levels or bacterial load between the 2 groups. Moreover, the bacterial targets of early IgA responses (including coating of the Bacteroides genus), as well as IgA recognition patterns, differed between healthy children and children with allergic manifestations. Altered IgA recognition patterns in children with allergy were observed already at 1 month of age, when the IgA antibodies are predominantly maternally derived in breast-fed children.

      Conclusion

      An aberrant IgA responsiveness to the gut microbiota during infancy precedes asthma and allergy development, possibly indicating an impaired mucosal barrier function in allergic children.

      Key words

      Abbreviations used:

      ARC (Allergic rhinoconjunctivitis), FITC (Fluorescein isothiocyanate), IgA+ (IgA-coated bacterial cells), IgA− (IgA-noncoated bacterial cells), LEfSe (Linear discriminant analysis effect size), qPCR (Quantitative PCR), PCA (Principal components analysis), RDP (Ribosomal Database Project), SIgA (Secretory IgA)
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