Abstract
BackgroundThe early gut microbiota has been proposed as an important link between environmental exposures and development of allergy‐related diseases. Beyond the widely investigated associations between the gut bacterial microbiota, we investigated the involvement of early gut mycobiota and gut permeability in the pathogenesis of asthma, allergic rhinoconjunctivitis (AR) and eczema.MethodsIn the Probiotics in the Prevention of Allergy among Children in Trondheim trial with maternal probiotic supplementation, we collected faecal samples at four timepoints between 0 and 2 years from a cohort of 278 children. Clinical information on allergy‐related diseases was collected in a paediatric examination at 2 years and questionnaires at 6 weeks and 1, 2 and 6 years. By quantitative PCR and 16S/ITS1 MiSeq rRNA gene sequencing, we analysed the gut bacterial and fungal microbiota abundance and bacterial diversity and explored associations with allergy‐related diseases. We also measured gut permeability markers (lipopolysaccharide‐binding protein [LBP] and fatty acid‐binding protein 2 [FABP2]).ResultsChildren with higher fungal abundance at 2 years were more likely to develop asthma and AR by 6 years, odds ratios 1.70 (95% CI: 1.06–2.75) and 1.41 (1.03–1.93), respectively. We explored causal connections, and children with eczema at 1–2 years appeared to have more mature bacterial microbiota, as well as being depleted of Enterococcus genus. Although LBP and FABP2 did not correlate with eczema, increased bacterial abundance was associated with increased serum FABP2.ConclusionsWe observed positive associations between gut fungal abundance and allergy‐related disease, but increased gut permeability does not appear to be involved in the underlying mechanisms for this association. Our findings should be confirmed in future microbiota studies.
Highlights
The early gut microbiota has been proposed as an important link between environmental exposures and development of allergy‐related diseases
We found a positive association between eczema up to 6 years and fungal abundance at 2 years, the confidence interval for this estimate was wide, and we cannot exclude that there is no association
We investigated the possible directions of causality for eczema by analysing whether fungal abundance was present before debut of allergic disease, or if allergic disease appeared before the increased fungal abundance (Figure 1)
Summary
The early gut microbiota has been proposed as an important link between environmental exposures and development of allergy‐related diseases. Allergy‐related diseases, such as asthma, allergic rhinoconjunctivitis (AR) and eczema, are chronic inflammatory diseases The prevalence of these diseases has increased over the last decades and collectively they are the most prevalent chronic diseases in childhood.[1] Environmental factors play an important role in the rising prevalence given the rapidity of its increase, and changing microbial exposures are suspected to be one of the driving factors.[2] The so‐called hygiene hypothesis originally postulated that reduced childhood infections may predispose to allergy‐related diseases; this hypothesis has evolved to place a greater emphasis on a depletion or perturbation of the early commensal microbiome and the influence of this disturbance on the developing immune system.[3,4]. Low bacterial diversity and varying microbial patterns have been shown to be associated with development of allergy‐related diseases later.[7,8,9] Whilet the gut microbiota mainly consists of bacteria, fungi colonise the gut
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