Gut microbial-derived butyrate is inversely associated with IgE responses to allergens in childhood asthma.

ABSTRACT

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 1 H-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, ß-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 ß-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 ß-alanine could be a specific biomarker connecting the metabolic dysbiosis of gut microbiota, Clostridium and Escherichia spp., in childhood asthma.