Temporal association of the development of oropharyngeal microbiota with early life wheeze in a population-based birth cohort

Abstract

Background A critical window in infancy has been proposed, during which the microbiota may affect subsequent health. The longitudinal development of the oropharyngeal microbiota is under-studied and may be associated with early-life wheeze. We aimed to investigate the temporal association of the development of the oropharyngeal microbiota with early-life wheeze. Methods A population-based birth cohort based in London, UK was followed for 24 months. We collected oropharyngeal swabs at six time-points. Microbiota was determined using sequencing of the V3-V5 region of the 16S rRNA-encoding gene. Medical records were reviewed for the outcome of doctor diagnosed wheeze. We used a time-varying model to investigate the temporal association between the development of microbiota and doctor-diagnosed wheeze. Findings 159 participants completed the study to 24 months and for 98 there was complete sequencing data at all timepoints and outcome data. Of these, 26 had doctor-diagnosed wheeze. We observed significant increase in the abundance of Neisseria between 9 and 24 months in children who developed wheeze ( p = 0∙003), while in those without wheezing there was a significant increment in the abundance of Granulicatella ( p = 0∙012) between 9 and 12 months, and of Prevotella (p = 0∙018) after 18 months. Interpretation A temporal association between the respiratory commensal Granulicatella and also Prevotella with wheeze (negative), and between Neisseria and wheeze (positive) was identified in infants prior to one year of age. This adds to evidence for the proposed role of the microbiota in the development of wheeze. Fund Research funding from the Winnicott Foundation, Meningitis Now and Micropathology Ltd.

Association of bacterial load in drinking water and allergic diseases in childhood

“…Our data indirectly support the notion of the important role of the gut microbiome. The overall evidence on gut microbiota suggests that a more rapid maturation is associated with decreased asthma risk and that specific genera may be associated with protection (including Veillonella, Lachnospira, Rothia and Bifidobacterium ), 30 whilst others (such as Moraxella 27 or Neisseria 31 ) increase the risk. Our findings in relation to eczema are consistent with studies which have demonstrated the importance of fecal microbiota in eczema 32 and the findings that relative abundance of immunomodulatory gut bacteria in the first year of life is associated with subsequent development of IgE‐associated eczema 33 …”

“…This suggests an early‐life “window of opportunity” when colonization has a potentially critical impact on health and disease 37,38 . The temporal changes in microbiota may be important, and recent study has shown that there may be a time window before age 1 year in which colonization of the oropharynx with Neisseria is positively, and with Granulicatella species negatively, associated with subsequent wheezing 31 …”

Airway bacterial carriage and childhood respiratory health: A population‐based prospective cohort study

“…We, however, did not observe an association of airway bacterial carriage with asthma at school age. Prospective cohort studies that used microbiome analyses showed an association of a high abundance of Streptococcus, but not Moraxella with wheeze at age 5 or 10 years 21,22 . Differences in findings, especially with regard to the association of hypopharyngeal bacterial carriage with lower respiratory tract infections and asthma between our study and the Danish study, might be explained by the higher prevalence of lower respiratory tract infections in their cohort and assessment of asthma at an earlier age.…”

Developmental patterns in the nasopharyngeal microbiome during infancy are associated with asthma risk

“…10,11 In addition, detection of specific bacteria by culture (Streptococcus pneumoniae, Moraxella catarrhalis, or Haemophilus influenzae) or 16S sequencing (eg, Prevotella, Veillonella) in oral or nasopharyngeal aspirates of babies have been related to asthma in early childhood. 2,12,13 In an Australian birth cohort (Childhood Asthma Study) using bacterial metagenomics based on 16S rRNA, predominance of S pneumoniae, M catarrhalis, or H influenzae was found to interact with early allergic sensitization to increase the risk of later asthma. 3,7 Others have found coassociation between eosinophil counts, severe RV bronchiolitis, and a Haemophilusor Moraxella-dominated profile of nasopharyngeal microbiota in infants.…”