ObjectivesA correct interpretation of sensitization to common allergens is critical in determining susceptibility to allergic diseases. The aim of this study was to investigate the patterns of sensitization to food and inhalant allergens, and their relation to the development of atopic diseases in early childhood.MethodsChildren aged 0 through 4 years from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Specific IgE antibody against food and inhalant allergens were measured and their association between total serum IgE levels and atopic diseases were assessed.ResultsA total of 182 children were regular followed up at clinics for a four-year follow-up period. The prevalence of food allergen sensitization increased markedly after 6 months of age, reaching up to 47% at 1.5 years of age and then declined significantly to 10% in parallel with a considerable increase in the prevalence of sensitization to inhalant allergens up to 25% at age 4. Food allergen sensitization appeared to be mainly associated with the elevation of serum total IgE levels before age 2. A combined sensitization to food and inhalant allergens had an additive effect on serum IgE levels after age 2, and was significantly associated with the risk of developing atopic diseases at age 4.ConclusionsSensitization to food occurs early in life, in parallel with the rising prevalence of sensitization to inhalant allergens at older age. A combined sensitization to food and inhalant allergens not only has an additive increase in serum IgE antibody production but also increases the risk of developing allergic respiratory diseases in early childhood.

Low maternal 25(OH)D levels appear not only to be associated with an increase in the prevalence of allergic sensitization but also the risk of eczema and asthma in early childhood.

ObjectivesA detailed understanding of the metabolic processes governing rapid growth in early life is still lacking. The aim of this study was to investigate the age-related metabolic changes in healthy children throughout early childhood.MethodsHealthy children from a birth cohort were enrolled in this study from birth through 4 years of age. Urinary metabolites were assessed at 6 months, and 1, 2, 3, and 4 yr of age by using 1H-nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate statistical analysis including principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). Metabolic pathway analysis was performed using the MetPA web tool.ResultsA total of 105 urine samples from 30 healthy children were collected and analyzed. Metabolites contributing to the discrimination between age groups were identified by using supervised PLS-DA (Q2 = 0.60; R2 = 0.66). A significantly higher urinary trimethylamine N-oxide (TMAO) and betaine level was found in children aged 6 months. Urinary glycine and glutamine levels declined significantly after 6 months of age and there was a concomitant compensatory increase in urinary creatine and creatinine. Metabolic pathway analysis using MetPA revealed similar nitrogen metabolism associated energy production across all ages assessed. Pathways associated with amino acid metabolism were significantly different between infants aged 6 months and 1 year, whereas pathways associated with carbohydrate metabolism were significantly different between children at ages 2 and 3 years.ConclusionsUrine metabolomics ideally represents dynamic metabolic changes across age. Urinary metabolic profiles change significantly within the first year of life, which can potentially provide crucial information about infant nutrition and growth.

Background There is increasing evidence linking alterations of the gut microbial composition during early infancy to the development of atopic diseases and asthma. However, few studies have addressed the association of dysbiotic gut microbiota with allergic reactions through evaluation of feces in young children with allergic airway diseases. Methods We sought to evaluate relationships among gut microbiota, total fecal immunoglobulin E (IgE) levels, serum allergic sensitization, and their relevance to childhood allergic rhinitis and asthma. Microbial composition and diversity were analyzed with Illumina-based 16S rRNA gene sequencing of 89 stool samples collected from children with asthma (n = 35) and allergic rhinitis (n = 28), and from healthy controls (n = 26). Data analysis was performed using Quantitative Insights into Microbial Ecology (QIIME) software. Results A significantly lower abundance of organisms of the phylum Firmicutes were found in children with asthma and allergic rhinitis than in the healthy controls. Relatively lower Chao1 and Shannon indices were also found in children with allergic airway diseases but without any significant difference. Total fecal IgE levels in early childhood were strongly correlated with serum D. pteronyssinus - and D. farinae -specific IgE but not with food-specific IgE levels. In comparison with healthy controls, the genus Dorea was less abundant and negatively correlated with total fecal IgE levels in children with rhinitis, whereas the genus Clostridium was abundant and positively correlated with fecal IgE levels in children with asthma. Conclusions An interaction between particular subsets of gut microbial dysbiosis and IgE-mediated responses to allergens may contribute to the susceptibility to allergic rhinitis and asthma in early childhood.

The interplay of the gut microbes with gut-producing nephrotoxins and the renal progression remains unclear in large human cohort. Significant compositional and functional differences in the intestinal microbiota (by 16S rRNA gene sequencing) were noted among 30 controls and 92 (31 mild, 30 moderate and 31 advanced) patients at different chronic kidney disease (CKD) stages (discovery cohort). A core CKD-associated microbiota consisted of 7 genera (Escherichia_Shigella, Dialister, Lachnospiraceae_ND3007_group, Pseudobutyrivibrio, Roseburia, Paraprevotella and Ruminiclostridium) and 2 species (Collinsella stercoris and Bacteroides eggerthii) were identified to be highly correlated with the stages of CKD. Paraprevotella, Pseudobutyrivibrio and Collinsella stercoris were superior in discriminating CKD from the controls than the use of urine protein/creatinine ratio, even at early-stage of disease. The performance was further confirmed in a validation cohort comprising 22 controls and 76 peritoneal dialysis patients. Bacterial genera highly correlated with indoxyl sulfate and p-cresyl sulfate levels were identified. Prediction of the functional capabilities of microbial communities showed that microbial genes related to the metabolism of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) were differentially enriched among the control and different CKD stages. Collectively, our results provide solid human evidence of the impact of gut-metabolite-kidney axis on the severity of chronic kidney disease and highlight a usefulness of specific gut microorganisms as possible disease differentiate marker of this global health burden.

Background A comprehensive metabolomics‐based approach to address the impact of specific gut microbiota on allergen sensitization for childhood rhinitis and asthma is still lacking. Methods Eighty‐five children with rhinitis (n = 27) and with asthma (n = 34) and healthy controls (n = 24) were enrolled. Fecal metabolomic analysis with 1H‐nuclear magnetic resonance (NMR) spectroscopy and microbiome composition analysis by bacterial 16S rRNA sequencing were performed. An integrative analysis of their associations with allergen‐specific IgE levels for allergic rhinitis and asthma was also assessed. Results Amino acid, β‐alanine, and butanoate were the predominant metabolic pathways in the gut. Among them, amino acid metabolism was negatively correlated with the phylum Firmicutes, which was significantly reduced in children with rhinitis and asthma. Levels of histidine and butyrate metabolites were significantly reduced in children with rhinitis (P = 0.029) and asthma (P = 0.009), respectively. In children with asthma, a reduction in butyrate‐producing bacteria, including Faecalibacterium and Roseburia spp., and an increase in Clostridium spp. were negatively correlated with fecal amino acids and butyrate, respectively (P < 0.01). Increased Escherichia spp. accompanied by increased β‐alanine and 4‐hydroxybutyrate appeared to reduce butyrate production. Low fecal butyrate was significantly associated with increased total serum and mite allergen–specific IgE levels in children with asthma (P < 0.05). Conclusion A reduced fecal butyrate is associated with increased mite‐specific IgE levels and the risk of asthma in early childhood. Fecal β‐alanine could be a specific biomarker connecting the metabolic dysbiosis of gut microbiota, Clostridium and Escherichia spp., in childhood asthma.

Subungual melanoma is a rare form of malignant melanoma. It is extremely difficult to differentiate it histologically from benign melanonychia striata or melanocytic nevus, especially in the early stage. We divided 50 cases of subungual melanoma into four groups according to clinical progress, and examined their histological findings in each respective stage. In the early stage (19 cases), atypical melanocytes were polygonal showing slight nuclear atypia with no mitoses at all. In six out of 19 cases (31.6%), the atypical melanocytes proliferated more in the hyponychium than in the nail matrix, and only very few in the nail bed. Periungual pigmentation (Hutchinson's sign) appeared from the early stage in almost all cases. With stage progression (middle stage, 13 cases; progressive stage, 13 cases; and bone invasive stage, five cases) the number of atypical melanocytes and their degree of nuclear atypia increased, and the ascent of atypical melanocytes and pagetoid spread became conspicuous. Mitoses became apparent only from the progressive stage. From these observations, we would like to propose three new pathological clues of early stage subungual melanoma: (i) “skip lesion”, proliferation of the tumor cells are more prominent in the hyponychium than in the nail bed or nail matrix; (ii) histological confirmation of Hutchinson's sign; and (iii) epithelial thickening and/or compact arrangement of the elongated basal cells.

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