A novel strategy to identify asthma-associated microbial clusters Reply

Non peer reviewe

Determinants of bacterial and fungal microbiota in Finnish home dust : Impact of environmental biodiversity, pets, and occupants

The indoors is where many humans spend most of their time, and are strongly exposed to indoor microbiota, which may have multifaceted effects on health. Therefore, a comprehensive understanding of the determinants of indoor microbiota is necessary. We collected dust samples from 295 homes of families with young children in the Helsinki region of Finland and analyzed the bacterial and fungal composition based on the 16S rRNA and ITS DNA sequences. Microbial profiles were combined with extensive survey data on family structure, daily life, and physical characteristics of the home, as well as additional external environmental information, such as land use, and vegetational biodiversity near the home. Using permutational multivariate analysis of variance we explained 18% of the variation of the relative abundance between samples within bacterial composition, and 17% of the fungal composition with the explanatory variables. The fungal community was dominated by the phyla Basidiomycota, and Ascomycota; the bacterial phyla Proteobacteria, Firmicutes, Cyanobacteria, and Actinobacteria were dominant. The presence of dogs, multiple children, and firewood were significantly associated with both the fungal and bacterial composition. Additionally, fungal communities were associated with land use, biodiversity in the area, and the type of building, while bacterial communities were associated with the human inhabitants and cleaning practices. A distinction emerged between members of Ascomycota and Basidiomycota, Ascomycota being more abundant in homes with greater surrounding natural environment, and potential contact with the environment. The results suggest that the fungal composition is strongly dependent on the transport of outdoor environmental fungi into homes, while bacteria are largely derived from the inhabitants.Peer reviewe

Determinants of bacterial and fungal microbiota in Finnish home dust : Impact of environmental biodiversity, pets, and occupants

The indoors is where many humans spend most of their time, and are strongly exposed to indoor microbiota, which may have multifaceted effects on health. Therefore, a comprehensive understanding of the determinants of indoor microbiota is necessary. We collected dust samples from 295 homes of families with young children in the Helsinki region of Finland and analyzed the bacterial and fungal composition based on the 16S rRNA and ITS DNA sequences. Microbial profiles were combined with extensive survey data on family structure, daily life, and physical characteristics of the home, as well as additional external environmental information, such as land use, and vegetational biodiversity near the home. Using permutational multivariate analysis of variance we explained 18% of the variation of the relative abundance between samples within bacterial composition, and 17% of the fungal composition with the explanatory variables. The fungal community was dominated by the phyla Basidiomycota, and Ascomycota; the bacterial phyla Proteobacteria, Firmicutes, Cyanobacteria, and Actinobacteria were dominant. The presence of dogs, multiple children, and firewood were significantly associated with both the fungal and bacterial composition. Additionally, fungal communities were associated with land use, biodiversity in the area, and the type of building, while bacterial communities were associated with the human inhabitants and cleaning practices. A distinction emerged between members of Ascomycota and Basidiomycota, Ascomycota being more abundant in homes with greater surrounding natural environment, and potential contact with the environment. The results suggest that the fungal composition is strongly dependent on the transport of outdoor environmental fungi into homes, while bacteria are largely derived from the inhabitants.Peer reviewe

Early-life residential exposure to moisture damage is associated with persistent wheezing in a Finnish birth cohort

Background and Aims Moisture damage increases the risk for respiratory disorders in childhood. Our aim was to determine whether early age residential exposure to inspector-observed moisture damage or mold is associated with different wheezing phenotypes later in childhood. Methods Building inspections were performed by civil engineers, in a standardized manner, in the children's homes-mostly single family and row houses (N = 344)-in the first year of life. The children were followed up with repeated questionnaires until the age of 6 years and wheezing phenotypes-never/infrequent, transient, intermediate, late onset, and persistent-were defined using latent class analyses. The multinomial logistic regression model was used for statistical analysis. Results A total of 63% (n = 218) had infrequent or no wheeze, 23% (n = 80) had transient and 9.6% (n = 21) had a persistent wheeze. Due to the low prevalence, results for intermediate (3.8%, n = 13) and late-onset wheeze (3.5%, n = 12) were not further evaluated. Most consistent associations were observed with the persistent wheeze phenotype with an adjusted odds ratio (95% confidence intervals) 2.04 (0.67-6.18) for minor moisture damage with or without mold spots (present in 23.8% of homes) and 3.68 (1.04-13.05) for major damage or any moisture damage with visible mold in a child's main living areas (present in 13.4% of homes). Early-age moisture damage or mold in the kitchen was associated with transient wheezing. Conclusion At an early age, residential exposure to moisture damage or mold, can be dose-dependently associated especially with persistent wheezing phenotype later in childhood.Peer reviewe

Excessive Unbalanced Meat Consumption in the First Year of Life Increases Asthma Risk in the PASTURE and LUKAS2 Birth Cohorts

A higher diversity of food items introduced in the first year of life has been inversely related to subsequent development of asthma. In the current analysis, we applied latent class analysis (LCA) to systematically assess feeding patterns and to relate them to asthma risk at school age. PASTURE (N=1133) and LUKAS2 (N=228) are prospective birth cohort studies designed to evaluate protective and risk factors for atopic diseases, including dietary patterns. Feeding practices were reported by parents in monthly diaries between the 4(th) and 12(th) month of life. For 17 common food items parents indicated frequency of feeding during the last 4 weeks in 4 categories. The resulting 153 ordinal variables were entered in a LCA. The intestinal microbiome was assessed at the age of 12 months by 16S rRNA sequencing. Data on feeding practice with at least one reported time point was available in 1042 of the 1133 recruited children. Best LCA model fit was achieved by the 4-class solution. One class showed an elevated risk of asthma at age 6 as compared to the other classes (adjusted odds ratio (aOR): 8.47, 95% CI 2.52-28.56, p = 0.001) and was characterized by daily meat consumption and rare consumption of milk and yoghurt. A refined LCA restricted to meat, milk, and yoghurt confirmed the asthma risk effect of a particular class in PASTURE and independently in LUKAS2, which we thus termed unbalanced meat consumption (UMC). The effect of UMC was particularly strong for non-atopic asthma and asthma irrespectively of early bronchitis (aOR: 17.0, 95% CI 5.2-56.1, p < 0.001). UMC fostered growth of iron scavenging bacteria such as Acinetobacter (aOR: 1.28, 95% CI 1.00-1.63, p = 0.048), which was also related to asthma (aOR: 1.55, 95% CI 1.18-2.03, p = 0.001). When reconstructing bacterial metabolic pathways from 16S rRNA sequencing data, biosynthesis of siderophore group nonribosomal peptides emerged as top hit (aOR: 1.58, 95% CI 1.13-2.19, p = 0.007). By a data-driven approach we found a pattern of overly meat consumption at the expense of other protein sources to confer risk of asthma. Microbiome analysis of fecal samples pointed towards overgrowth of iron-dependent bacteria and bacterial iron metabolism as a potential explanation.Peer reviewe

Association between antibiotic treatment during pregnancy and infancy and the development of allergic diseases

Background: Allergies are a serious public health issue, and prevalences are rising worldwide. The role of antibiotics in the development of allergies has repeatedly been discussed, as results remain inconsistent. The aim of this study was to investigate the association between pre-and post-natal antibiotic exposure and subsequent development of allergies (atopic dermatitis, food allergy, asthma, atopic sensitization and allergic rhinitis). Methods: A total of 1080 children who participated in a European birth cohort study (PASTURE) were included in this analysis. Data on antibiotic exposure during pregnancy and/or first year of life and allergic diseases were collected by questionnaires from pregnancy up to 6 years of age and analysed by performing logistic regressions. To take into account reverse causation, we included models, where children with diagnosis or symptoms of the respective disease in the first year of life were excluded. Results: Antibiotic exposure in utero was significantly and positively associated with atopic dermatitis and food allergy. The strongest effect was on diseases with onset within the first year of life (for atopic dermatitis: aOR 1.66, 95% CI 1.11-2.48 and for food allergy: aOR 3.01, 95% CI 1.22-7.47). Antibiotics in the first year of life were positively associated with atopic dermatitis up to 4 years (aOR 2.73, 95% CI 1.66-4.49) and also suggested a dose-response relationship. A tendency was observed with asthma between 3 and 6 years (aOR 1.65, 95% CI 0.95-2.86). Conclusions: Our findings show positive associations between exposure to antibiotics and allergies, mainly atopic dermatitis and food allergy within the first year of life, after prenatal exposure, and atopic dermatitis and asthma after post-natal exposure to antibiotics in children born in rural settings.Peer reviewe

Crawling-induced floor dust resuspension affects the microbiota of the infant breathing zone

Background: Floor dust is commonly used for microbial determinations in epidemiological studies to estimate early-life indoor microbial exposures. Resuspension of floor dust and its impact on infant microbial exposure is, however, little explored. The aim of our study was to investigate how floor dust resuspension induced by an infant's crawling motion and an adult walking affects infant inhalation exposure to microbes. Results: We conducted controlled chamber experiments with a simplified mechanical crawling infant robot and an adult volunteer walking over carpeted flooring. We applied bacterial 16S rRNA gene sequencing and quantitative PCR to monitor the infant breathing zone microbial content and compared that to the adult breathing zone and the carpet dust as the source. During crawling, fungal and bacterial levels were, on average, 8- to 21-fold higher in the infant breathing zone compared to measurements from the adult breathing zone. During walking experiments, the increase in microbial levels in the infant breathing zone was far less pronounced. The correlation in rank orders of microbial levels in the carpet dust and the corresponding infant breathing zone sample varied between different microbial groups but was mostly moderate. The relative abundance of bacterial taxa was characteristically distinct in carpet dust and infant and adult breathing zones during the infant crawling experiments. Bacterial diversity in carpet dust and the infant breathing zone did not correlate significantly. Conclusions: The microbiota in the infant breathing zone differ in absolute quantitative and compositional terms from that of the adult breathing zone and of floor dust. Crawling induces resuspension of floor dust from carpeted flooring, creating a concentrated and localized cloud of microbial content around the infant. Thus, the microbial exposure of infants following dust resuspension is difficult to predict based on common house dust or bulk air measurements. Improved approaches for the assessment of infant microbial exposure, such as sampling at the infant breathing zone level, are needed.Peer reviewe

Early age exposure to moisture and mould is related to FeNO at the age of 6 years

Background Exposure to indoor moisture damage and visible mold has been found to be associated with asthma and respiratory symptoms in several questionnaire-based studies by self-report. We aimed to define the prospective association between the early life exposure to residential moisture damage or mold and fractional exhaled nitric oxide (FeNO) and lung function parameters as objective markers for airway inflammation and asthma in 6-year-old children. Methods Home inspections were performed in children's homes when infants were on average 5 months old. At age 6 years, data on FeNO (n = 322) as well as lung function (n = 216) measurements were collected. Logistic regression and generalized additive models were used for statistical analyses. Results Early age major moisture damage and moisture damage or mold in the child's main living areas were significantly associated with increased FeNO levels (>75th percentile) at the age of 6 years (adjusted odds ratios, 95% confidence intervals, aOR (95% CI): 3.10 (1.35-7.07) and 3.16 (1.43-6.98), respectively. Effects were more pronounced in those who did not change residential address throughout the study period. For lung function, major structural damage within the whole home was associated with reduced FEV1 and FVC, but not with FEV1/FVC. No association with lung function was observed with early moisture damage or mold in the child's main living areas. Conclusion These results underline the importance of prevention and remediation efforts of moisture and mold-damaged buildings in order to avoid harmful effects within the vulnerable phase of the infants and children's immunologic development.Peer reviewe

Indoor bacterial microbiota and development of asthma by 10.5 years of age

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 > vertical bar 0.4 vertical bar) 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.Peer reviewe