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.

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 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.

Several metabolomics studies have identified altered metabolic pathways that are related to asthma. However, an integrative analysis of the metabolic responses across blood and urine for a comprehensive framework of asthma in early childhood remains lacking. Fifty-four age-matched children with asthma (n = 28) and healthy controls (n = 26) were enrolled. Metabolome analysis of the plasma and urine samples was performed using 1H-nuclear magnetic resonance (NMR) spectroscopy coupled with partial least-squares discriminant analysis (PLS-DA). Integrated analysis of blood and urine metabolic profiling related to IgE reactions for childhood asthma was investigated. A significantly higher plasma histidine level was found, in parallel with lower urinary 1-methylnicotinamide and trimethylamine N-oxide (TMAO) levels, in children with asthma compared to healthy controls. Compared to children without allergic sensitization, 11 (92%) plasma metabolites and 8 (80%) urinary metabolites were found to be significantly different in children with IgE and food sensitization respectively. There were significant correlations between the plasma 3-hydroxybutyric acid and excreted volumes of the hydroxy acids, which were strongly correlated to plasma leucine and valine levels. Urine N-phenylacetylglycine, a microbial-host co-metabolite, was strongly correlated with total serum and food allergen-specific IgE levels. Plasma pyruvate and urine valine, leucine, and isoleucine degradation metabolisms were significantly associated with allergic sensitization for childhood asthma. In conclusion, blood and urine metabolome reflect different metabolic pathways in allergic reactions. Plasma pyruvate metabolism to acetic acid appears to be associated with serum IgE production, whereas urine branched-chain amino acid metabolism primarily reflects food allergic reactions against allergies.

Longitudinal urinary metabolomic profiling provides a link of microbe-environment interactions in the development of childhood asthma. 1-Methylnicotinamide and allantoin may participate in allergic reactions in response to allergen exposure, potentially serving as specific biomarkers for asthma.

Metabolic markers in biofluids represent an attractive tool for guiding clinical management. The aim of this study was to identify metabolic mechanisms during the progress of pleural infection in children with Streptococcus pneumoniae pneumonia. Forty children diagnosed with pneumococcal pneumonia were enrolled and analysis of pleural fluid metabolites categorized by complicated parapneumonic effusions (CPE) and non-CPE was assessed by using 1H-NMR spectroscopy. Multivariate statistical analysis including principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were performed. Metabolites identified were studied in relation to subsequent intervention procedures by receiver operating characteristic (ROC) curve analysis. Ten metabolites significantly different between CPE and non-CPE were identified. A significantly lower level of glucose for glycolysis was found in CPE compared to non-CPE. Six metabolites involving bacterial biosynthesis and three metabolites involving bacterial fermentation were significantly higher in CPE compared to non-CPE. Glucose and 3-hydroxybutyric acid were the metabolites found to be useful in discriminating from receiving intervention procedures. Metabolic profiling of pleural fluid using 1H-NMR spectroscopy provides direct observation of bacterial metabolism in the progress of pneumococcal pneumonia. An increase in the metabolism of butyric acid fermentation of glucose could potentially lead to the need of aggressive pleural drainage.

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A connection between airway and gut microbiota related to allergen exposure in childhood allergies was not well addressed. We aimed to identify the microbiota alterations in the airway and gut related to mite-specific IgE responses in young children with airway allergies. This study enrolled 60 children, including 38 mite-sensitized children (20 rhinitis and 18 asthma), and 22 non-mite-sensitized healthy controls. Microbiome composition analysis of the throat swab and stool samples was performed using bacterial 16S rRNA sequencing. An integrative analysis of the airway and stool microbial profiling associated with IgE reactions in childhood allergic rhinitis and asthma was examined. The Chao1 and Shannon indices in the airway were significantly lower than those in the stool. Additionally, an inverse association of the airway microbial diversity with house dust mite (HDM) sensitization and allergic airway diseases was noted. Fecal IgE levels were positively correlated with the serum Dermatophagoides pteronyssinus-and Dermatophagoides farinae-specific IgE levels. Airway Leptotrichia spp. related to asthma were strongly correlated with fecal Dorea and Ruminococcus spp., which were inversely associated with fecal IgE levels and risk of allergic rhinitis. Moreover, four airway genera, Campylobacter, Selenomonas, Tannerella, and Atopobium, were negatively correlated with both serum mite-specific and fecal IgE levels. Among them, the airway Selenomonas and Atopobium spp. were positively correlated with stool Blautia and Dorea spp. related to asthma and allergic rhinitis, respectively. In conclusion, airway microbial dysbiosis in response to HDM and its cross-talk with the gut microbial community is related to allergic airway diseases in early childhood. Dysbiosis in the gut microbiota is associated with several respiratory infections and lung diseases, including allergy and asthma 1,2. There is accumulating evidence that a cross-talk exists between gut and lung. The upper gastrointestinal microbiota affects the development of the airway microbiota either by aspiration or metabolite production, leading to changes in the airway microenvironment 3. Conversely, the dysbiosis in the lung microbiota is accompanied by that in the gut microbiota via bloodstream 4. In a recent study, airway microbial dysbiosis appears to be strongly associated with sensitization to house dust mites (HDM), potentially contributing to allergic reactions and airway diseases 5. However, its contribution to the gut-lung axis associated with allergies remains unclear. HDM allergy with an elevated immunoglobulin E (IgE) level is strongly implicated in the allergic rhinitis and asthma pathogeneses in children 6. Clinically, the comorbidity between these two conditions is high for perennial aeroallergens 7,8. Furthermore, IgE is also produced locally in the gut and fecal IgE level could serve as a marker