Environmental and occupational disease
Indoor bacterial microbiota and development of asthma by 10.5 years of age

https://doi.org/10.1016/j.jaci.2019.07.035Get rights and content

Background

Early-life indoor bacterial exposure is associated with the risk of asthma, but the roles of specific bacterial genera are poorly understood.

Objective

We sought to determine whether individual bacterial genera in indoor microbiota predict the development of asthma.

Methods

Dust samples from living rooms were collected at 2 months of age. The dust microbiota was characterized by using Illumina MiSeq sequencing amplicons of the bacterial 16S ribosomal RNA gene. Children (n = 373) were followed up for ever asthma until the age of 10.5 years.

Results

Richness was inversely associated with asthma after adjustments (P = .03). The phylogenetic microbiota composition in asthmatics patients' homes was characteristically different from that in nonasthmatic subjects' homes (P = .02, weighted UniFrac, adjusted association, permutational multivariate analysis of variance, PERMANOVA-S). The first 2 axis scores of principal coordinate analysis of the weighted UniFrac distance matrix were inversely associated with asthma. Of 658 genera detected in the dust samples, the relative abundances of 41 genera correlated (r > |0.4|) with one of these axes. Lactococcus genus was a risk factor for asthma (adjusted odds ratio, 1.36 [95% CI, 1.13-1.63] per interquartile range change). The abundance of 12 bacterial genera (mostly from the Actinomycetales order) was associated with lower asthma risk (P < .10), although not independently of each other. The sum relative abundance of these 12 intercorrelated genera was significantly protective and explained the majority of the association of richness with less asthma.

Conclusion

Our data confirm that phylogenetic differences in the microbiota of infants' homes are associated with subsequent asthma risk and suggest that communities of selected bacteria are more strongly linked to asthma protection than individual bacterial taxa or mere richness.

Section snippets

Methods

The study population consisted of children born in middle and eastern Finland: the first half of the study population (n = 214) belonged to a European birth cohort (Protection Against Allergy Study in Rural Environments [PASTURE])18 among farmers and nonfarmers, whereas the second half of the cohort consisted of unselected children (n = 228).19 Pregnant women who gave birth between September 2002 and May 2005 were recruited. The selection procedure has been described earlier, and the study

Results

Of the 442 children, 394 (89.1%) had data on the bacterial microbiota in dust samples, and 373 (94.6%) of those had sufficient data to assess asthma until the age of 10.5 years and information on covariates. By the age of 10.5 years, 69 (18.5%) children had ever asthma, and 29 (7.8%) had current asthma at 10.5 years.

Discussion

The present study suggests that phylogenetic differences in the early home indoor microbiota composition precede asthma development, and this association is not explained by bacterial richness alone. Of 658 genera detected in dust samples, only the relative abundance of Lactococcus genus was determined as an independent risk factor for asthma. Twelve bacterial genera (mostly from the order Actinomycetales) were identified as protective. The sum of the relative abundance of these 12 protective

References (38)

  • E. von Mutius et al.

    Farm living: effects on childhood asthma and allergy

    Nat Rev Immunol

    (2010)
  • C. Braun-Fahrländer et al.

    Environmental exposure to endotoxin and its relation to asthma in school-age children

    N Engl J Med

    (2002)
  • C. Tischer et al.

    Early exposure to bio-contaminants and asthma up to 10 years of age: results of the HITEA study

    Eur Respir J

    (2015)
  • J.E. Sordillo et al.

    Multiple microbial exposures in the home may protect against asthma or allergy in childhood

    Clin Exp Allergy

    (2010)
  • A.M. Karvonen et al.

    Exposure to microbial agents in house dust and wheezing, atopic dermatitis and atopic sensitization in early childhood: a birth cohort study in rural areas

    Clin Exp Allergy

    (2012)
  • V. Doreswamy et al.

    Modulation of asthma by endotoxin

    Clin Exp Allergy

    (2011)
  • A.M. Karvonen et al.

    Quantity and diversity of environmental microbial exposure and development of asthma: a birth cohort study

    Allergy

    (2014)
  • M.J. Ege et al.

    Exposure to environmental microorganisms and childhood asthma

    N Engl J Med

    (2011)
  • K.C. Dannemiller et al.

    Next-generation DNA sequencing reveals that low fungal diversity in house dust is associated with childhood asthma development

    Indoor Air

    (2014)
  • Cited by (0)

    Supported by research grants from the Academy of Finland (grants 139021, 287675, 296814, 296817, and 308254), the Juho Vainio Foundation, the Yrjö Jahnsson Foundation, the Foundation for Pediatric Research, EVO/VTR-funding, the Päivikki and Sakari Sohlberg Foundation, the Finnish Cultural Foundation, the European Union (QLK4-CT-2001-00250), and the Finnish Institute for Health and Welfare, Finland.

    Disclosure of potential conflict of interest: A. M. Karvonen and J. Pekkanen report grants from the Academy of Finland, the Juho Vainio Foundation, the Yrjö Jahnsson Foundation, the Foundation for Pediatric Research, EVO/VTR-funding, the Päivikki and Sakari Sohlberg Foundation, the Finnish Cultural Foundation, and the European Union during the conduct of the study. P. V. Kirjavainen reports grants from Päivikki and the Sakari Sohlberg Foundation, the Yrjö Jahnsson Foundation, the Nutricia Research Foundation, the Juho Vainio Foundation, and the Academy of Finland during the conduct of the study. E. von Mutius reports grants from the European Commission during the conduct of the study and personal fees from PharmaVentures, OM Pharma, Decision Resources, Novartis Pharma SAS (Rueil-Malmaison, France), the Chinese University of Hong Kong, the University of Copenhagen, HAL Allergie GmbH, Ökosoziales Forum Oberösterreich, Mundipharma, the American Thoracic Society, AbbVie Deutschland GmbH & Co. KG, the University of Tampere, the European Commission, the Massachusetts Medical Society, and the American Academy of Allergy, Asthma & Immunology outside the submitted work; also, E. von Mutius is listed as inventor on the patents “Composition containing bacterial antigens used for the prophylaxis and the treatment of allergic diseases” (publication no. EP 1411977), “Stable dust extract for allergy protection” (publication no. EP1637147), “Pharmaceutical compound to protect against allergies and inflammatory diseases” (publication no. EP 1964570), and “Barn dust extract for the prevention and treatment of diseases” (application no. LU101064 [pending], and she is listed as inventor and has received royalties on the patent “Specific environmental bacteria for the protection from and/or the treatment of allergic, chronic inflammatory and/or autoimmune disorders” (publication no. EP2361632). The rest of the authors declare that they have no relevant conflicts of interest.

    View full text