ABSTRACT
Although the nose, as a gateway for organism-environment interactions, may have a key role in asthmatic exacerbation, the rhinobiome of exacerbated children with asthma was widely neglected to date. The aim of this study is to understand the microbiome, the microbial immunology, and the proteome of exacerbated children and adolescents with wheeze and asthma. Considering that a certain proportion of wheezers may show a progression to asthma, the comparison of both groups provides important information regarding clinical and phenotype stratification. Thus, deep nasopharyngeal swab specimens, nasal epithelial spheroid (NAEsp) cultures, and blood samples of acute exacerbated wheezers (WH), asthmatics (AB), and healthy controls (HC) were used for culture (n = 146), 16 S-rRNA gene amplicon sequencing (n = 64), and proteomic and cytokine analyses. Interestingly, Proteobacteria were over-represented in WH, whereas Firmicutes and Bacteroidetes were associated with AB. In contrast, Actinobacteria commonly colonized HCs. Moreover, Staphylococcaceae, Enterobacteriaceae, Burkholderiaceae, Xanthobacteraceae, and Sphingomonadaceae were significantly more abundant in AB compared to WH and HC. The α-diversity analyses demonstrated an increase of bacterial abundance levels in atopic AB and a decrease in WH samples. Microbiome profiles of atopic WH differed significantly from atopic AB, whereby atopic samples of WH were more homogeneous than those of non-atopic subjects. The NAEsp bacterial exposure experiments provided a disrupted epithelial cell integrity, a cytokine release, and cohort-specific proteomic differences especially for Moraxella catarrhalis cultures. This comprehensive dataset contributes to a deeper insight into the poorly understood plasticity of the nasal microbiota, and, in particular, may enforce our understanding in the pathogenesis of asthma exacerbation in childhood.
ABSTRACT
In the intestinal mucosa trefoil factors (TFF) and mucins (Muc) - primarily produced by goblet cells - are thought to play a major role in providing barrier function during infection and inflammation. To investigate their role in pediatric Crohn's disease (CD) and ulcerative colitis (UC) we obtained mucosal biopsies of children with CD, UC and healthy controls and analyzed genetic expression. Levels of TFF2 mRNA were lower in inflamed mucosal samples (terminal ileum (TI) and duodenum) of children with CD, but higher in non-inflamed mucosal samples when compared to healthy controls (p < 0.05). Similarly, TFF2 levels in the TI were significantly lower in inflamed UC tissue. Adjustment for goblet cell density revealed slightly less marked, yet significantly different gene expression in IBD and controls. Furthermore, TI expression of TFF2 and Muc2 was inversely correlated with interleukin-8 expression in CD (p = 0.027). In Summary, our data demonstrate significant changes in Muc and TFF mRNA expression in pediatric patients with IBD suggesting a role in mucosal healing. Further studies are needed to elucidate a potential use as biomarkers for disease progression.
Subject(s)
Inflammatory Bowel Diseases/metabolism , Intestinal Mucosa/metabolism , Mucins/metabolism , Peptides/metabolism , Adolescent , Biomarkers/metabolism , Child , Female , Humans , Male , Reproducibility of Results , Sensitivity and Specificity , Tissue Distribution , Trefoil Factor-2ABSTRACT
The need to rationalise teaching resources underpinned a project at Monash University that used a Delphi technique to re-examine the teaching curriculum of two key topic areas in the medical curriculum - ophthalmology and dermatology - from an undergraduate, graduate and vocational perspective. Using Bloom's taxonomy the learning objectives from these topic areas were collated and analysed. This process allowed the revising and redistributing of learning objectives of the curricula to reduce the likelihood of duplication of teaching or more importantly gaps in teaching occurring. This process highlighted the potential utility of using a transgenerational approach to curriculum planning but the outcomes are limited due to the small number of participating educators and the lack of formal evaluation of the method.
