Farm-like indoor microbiota in non-farm homes protects children from asthma development

Asthma prevalence has increased in epidemic proportions with urbanization, but growing up on traditional farms offers protection even today(1). The asthma-protective effect of farms appears to be associated with rich home dust microbiota(2,3), 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(4) 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(2) 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.Peer reviewe

Patterns of Genome-Wide VDR Locations

<div><p>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. <i>De novo</i> 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.</p></div

DR3-type sequences in VDR ChIP-seq peaks.

<p><b>A </b><i>De novo</i> analysis was performed on sequences below VDR peaks (±100 bp) of stimulated (stim) and unstimulated (unstim) datasets from LPS-differentiated THP-1 cells (THP-1,LPS), undifferentiated THP-1 cells, the lymphoblastoid cell lines GM10855 and GM10861, LX2 cells and LS180 cells. The sequence logos of DR3-type sequences are indicated, with the match score for the motif against the HOMER-native reference for the DR3-type sequence (range: 0–1). <b>B</b> HOMER was used, with variable thresholds, to screen for the representative DR3-type sequence, i.e. that from stimulated, undifferentiated THP-1 cells, in the same 12 datasets of sequences below VDR peaks. The percentage of identified DR3-type sequences are displayed as a function of the used HOMER scores. The grey box highlights the HOMER score for the representative DR3-type sequence (9.184643) that was used for the plot in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096105#pone-0096105-g004" target="_blank">Fig. 4</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096105#pone.0096105.s007" target="_blank">Table S1</a>. <b>C</b> The density of the representative DR3-type sequence is displayed ±500 bp around the peak summits. For clarity, the stimulated (left panel) and unstimulated (right panel) samples are displayed separately. The gray boxes delineate the ±100 bp region around the peak summits.</p