Asthma prevalence has increased in epidemic proportions with urbanization, but growing up on traditional farms offers protection even today
. The asthma-protective effect of farms appears to be ...associated with rich home dust microbiota
, which could be used to model a health-promoting indoor microbiome. Here we show by modeling differences in house dust microbiota composition between farm and non-farm homes of Finnish birth cohorts
that in children who grow up in non-farm homes, asthma risk decreases as the similarity of their home bacterial microbiota composition to that of farm homes increases. The protective microbiota had a low abundance of Streptococcaceae relative to outdoor-associated bacterial taxa. The protective effect was independent of richness and total bacterial load and was associated with reduced proinflammatory cytokine responses against bacterial cell wall components ex vivo. We were able to reproduce these findings in a study among rural German children
and showed that children living in German non-farm homes with an indoor microbiota more similar to Finnish farm homes have decreased asthma risk. The indoor dust microbiota composition appears to be a definable, reproducible predictor of asthma risk and a potential modifiable target for asthma prevention.
Living with dogs appears to protect against allergic diseases and airway infections, an effect possibly linked with immunomodulation by microbial exposures associated with dogs. The aim of this study ...was to characterize the influence of dog ownership on house dust microbiota composition. The bacterial and fungal microbiota was characterized with Illumina MiSeq sequencing from floor dust samples collected from homes in a Finnish rural-suburban (LUKAS2, N = 182) birth cohort, and the results were replicated in a German urban (LISA, N = 284) birth cohort. Human associated bacteria variable was created by summing up the relative abundances of five bacterial taxa. Bacterial richness, Shannon index and the relative abundances of seven bacterial genera, mostly within the phyla Proteobacteria and Firmicutes, were significantly higher in the dog than in the non-dog homes, whereas the relative abundance of human associated bacteria was lower. The results were largely replicated in LISA. Fungal microbiota richness and abundance of Leucosporidiella genus were higher in dog homes in LUKAS2 and the latter association replicated in LISA. Our study confirms that dog ownership is reproducibly associated with increased bacterial richness and diversity in house dust and identifies specific dog ownership-associated genera. Dogs appeared to have more limited influence on the fungal than bacterial indoor microbiota.
Abstract
Phospholipids, such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC), are the major components of cell membranes. Their exposure to reactive oxygen species creates oxidized ...phospholipids, which predispose to the development of chronic inflammatory diseases and metabolic disorders through endothelial activation and dysfunction. Although the effects of oxidized PAPC (oxPAPC) on endothelial cells have been previously studied, the underlying molecular mechanisms evoking biological responses remain largely unknown. Here, we investigated the molecular mechanisms of oxPAPC function with a special emphasis on NRF2-regulated microRNAs (miRNAs) in human umbilical vein endothelial cells (HUVECs) utilizing miRNA profiling, global run-on sequencing (GRO-seq), genome-wide NRF2 binding model, and RNA sequencing (RNA-seq) with miRNA overexpression and silencing. We report that the central regulators of endothelial activity, KLF2 for quiescence, PFKFB3 for glycolysis, and VEGFA, FOXO1 and MYC for growth and proliferation, are regulated by transcription factor NRF2 and the NRF2-regulated miR-106b∼25 cluster member, miR-93, in HUVECs. Mechanistically, oxPAPC was found to induce glycolysis and proliferation NRF2-dependently, and oxPAPC-dependent induction of the miR-106b∼25 cluster was mediated by NRF2. Additionally, several regulatory loops were established between NRF2, miR-93 and the essential regulators of healthy endothelium, collectively implying that NRF2 controls the switch between the quiescent and the proliferative endothelial states together with miR-93.
Microbial exposures in early childhood direct the development of the immune system and their diversity may influence the risk of allergy development. We aimed to determine whether the indoor ...microbial diversity at early-life is associated with the development of allergic rhinitis and inhalant atopy.
The study population included children within two birth cohorts: Finnish rural-suburban LUKAS (N = 312), and German urban LISA from Munich and Leipzig study centers (N = 248). The indoor microbiota diversity (Chao1 richness and Shannon entropy) was characterized from floor dust samples collected at the child age of 2–3 months by Illumina MiSeq sequencing of bacterial and fungal DNA amplicons. Allergic rhinitis and inhalant atopy were determined at the age of 10 years and analyzed using logistic regression models.
High bacterial richness (aOR 0.19, 95%CI 0.09–0.42 for middle and aOR 0.12, 95%CI 0.05–0.29 for highest vs. lowest tertile) and Shannon entropy were associated with lower risk of allergic rhinitis in LISA, and similar trend was seen in LUKAS. We observed some significant associations between bacterial and fungal diversity measured and the risk of inhalant atopy, but the associations were inconsistent between the two cohorts. High bacterial diversity tended to be associated with increased risk of inhalant atopy in rural areas, but lower risk in more urban areas. Fungal diversity tended to be associated with increased risk of inhalant atopy only in LISA.
Our study suggests that a higher bacterial diversity may reduce the risk of allergic rhinitis later in childhood. The environment-dependent heterogeneity in the associations with inhalant atopy – visible here as inconsistent results between two differing cohorts - suggests that specific constituents of the diversity may be relevant.
•Effects of microbial exposures were studied in two birth cohorts and countries.•High bacterial diversity in early-life home may protect against allergic rhinitis.•Effects of microbial diversity on inhalant atopy varied per environment and cohort.
The genome-wide analysis of the binding sites of the transcription factor vitamin D receptor (VDR) is essential for a global appreciation the physiological impact of the nuclear hormone ...1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Genome-wide analysis of lipopolysaccharide (LPS)-polarized THP-1 human monocytic leukemia cells via chromatin immunoprecipitation sequencing (ChIP-seq) resulted in 1,318 high-confidence VDR binding sites, of which 789 and 364 occurred uniquely with and without 1,25(OH)2D3 stimulation, while only 165 were common. We re-analyzed five public VDR ChIP-seq datasets with identical peak calling settings (MACS, version 2) and found, using a novel consensus summit identification strategy, in total 23,409 non-overlapping VDR binding sites, 75% of which are unique within the six analyzed cellular models. LPS-differentiated THP-1 cells have 22% more genomic VDR locations than undifferentiated cells and both cell types display more overlap in their VDR locations than the other investigated cell types. In general, the intersection of VDR binding profiles of ligand-stimulated cells is higher than those of unstimulated cells. De novo binding site searches and HOMER screening for binding motifs formed by direct repeats spaced by three nucleotides (DR3) suggest for all six VDR ChIP-seq datasets that these sequences are found preferentially at highly ligand responsive VDR loci. Importantly, all VDR ChIP-seq datasets display the same relationship between the VDR occupancy and the percentage of DR3-type sequences below the peak summits. The comparative analysis of six VDR ChIP-seq datasets demonstrated that the mechanistic basis for the action of the VDR is independent of the cell type. Only the minority of genome-wide VDR binding sites contains a DR3-type sequence. Moreover, the total number of identified VDR binding sites in each ligand-stimulated cell line inversely correlates with the percentage of peak summits with DR3 sites.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Urban‐related nature exposures are suggested to contribute to the rising prevalence of allergic diseases despite little supporting evidence. Our aim was to evaluate the impact of 12 land ...cover classes and two greenness indices around homes at birth on the development of doctor‐diagnosed eczema by the age of 2 years, and the influence of birth season.
Methods
Data from 5085 children were obtained from six Finnish birth cohorts. Exposures were provided by the Coordination of Information on the Environment in three predefined grid sizes. Adjusted logistic regression was run in each cohort, and pooled effects across cohorts were estimated using fixed or random effect meta‐analyses.
Results
In meta‐analyses, neither greenness indices (NDVI or VCDI, 250 m × 250 m grid size) nor residential or industrial/commercial areas were associated with eczema by age of 2 years. Coniferous forest (adjusted odds ratio 1.19; 95% confidence interval 1.01–1.39 for the middle and 1.16; 0.98–1.28 for the highest vs. lowest tertile) and mixed forest (1.21; 1.02–1.42 middle vs. lowest tertile) were associated with elevated eczema risk. Higher coverage with agricultural areas tended to associate with elevated eczema risk (1.20; 0.98–1.48 vs. none). In contrast, transport infrastructure was inversely associated with eczema (0.77; 0.65–0.91 highest vs. lowest tertile).
Conclusion
Greenness around the home during early childhood does not seem to protect from eczema. In contrast, nearby coniferous and mixed forests may increase eczema risk, as well as being born in spring close to forest or high‐green areas.
BackgroundUrban‐related nature exposures are suggested to contribute to the rising prevalence of allergic diseases despite little supporting evidence. Our aim was to evaluate the impact of 12 land ...cover classes and two greenness indices around homes at birth on the development of doctor‐diagnosed eczema by the age of 2 years, and the influence of birth season.MethodsData from 5085 children were obtained from six Finnish birth cohorts. Exposures were provided by the Coordination of Information on the Environment in three predefined grid sizes. Adjusted logistic regression was run in each cohort, and pooled effects across cohorts were estimated using fixed or random effect meta‐analyses.ResultsIn meta‐analyses, neither greenness indices (NDVI or VCDI, 250 m × 250 m grid size) nor residential or industrial/commercial areas were associated with eczema by age of 2 years. Coniferous forest (adjusted odds ratio 1.19; 95% confidence interval 1.01–1.39 for the middle and 1.16; 0.98–1.28 for the highest vs. lowest tertile) and mixed forest (1.21; 1.02–1.42 middle vs. lowest tertile) were associated with elevated eczema risk. Higher coverage with agricultural areas tended to associate with elevated eczema risk (1.20; 0.98–1.48 vs. none). In contrast, transport infrastructure was inversely associated with eczema (0.77; 0.65–0.91 highest vs. lowest tertile).ConclusionGreenness around the home during early childhood does not seem to protect from eczema. In contrast, nearby coniferous and mixed forests may increase eczema risk, as well as being born in spring close to forest or high‐green areas.
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