Division of Pediatric Pulmonology, Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, and Chang Gung University, Taoyuan, Taiwan.
Department of Biomedical Sciences, and Metabolomics Core Laboratory, Healthy Aging Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Pediatr Allergy Immunol. 2019 Nov;30(7):689-697. doi: 10.1111/pai.13096. Epub 2019 Jul 9.
A comprehensive metabolomics-based approach to address the impact of specific gut microbiota on allergen sensitization for childhood rhinitis and asthma is still lacking.
Eighty-five children with rhinitis (n = 27) and with asthma (n = 34) and healthy controls (n = 24) were enrolled. Fecal metabolomic analysis with 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.
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).
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.
目前仍缺乏一种基于全面代谢组学的方法来研究特定肠道微生物群对儿童变应性鼻炎和哮喘致敏的影响。
共纳入 85 名患有鼻炎（n=27）、哮喘（n=34）和健康对照（n=24）的儿童。采用 H-核磁共振（NMR）光谱进行粪便代谢组学分析，采用细菌 16S rRNA 测序进行微生物组组成分析。还评估了它们与变应性鼻炎和哮喘过敏原特异性 IgE 水平之间的关联的综合分析。
氨基酸、β-丙氨酸和丁酸盐是肠道中的主要代谢途径。其中，氨基酸代谢与厚壁菌门呈负相关，而厚壁菌门在患有鼻炎和哮喘的儿童中显著减少。组氨酸和丁酸盐代谢物的水平在患有鼻炎的儿童中显著降低（P=0.029）和哮喘（P=0.009）。在患有哮喘的儿童中，丁酸产生菌（包括粪杆菌和罗斯伯里氏菌属）减少，梭菌属增加，与粪便氨基酸和丁酸呈负相关（P<0.01）。增加的大肠杆菌属伴随着β-丙氨酸和 4-羟丁酸的增加，似乎减少了丁酸的产生。低粪便丁酸与哮喘儿童总血清和螨过敏原特异性 IgE 水平增加显著相关（P<0.05）。
粪便丁酸减少与螨特异性 IgE 水平升高和儿童哮喘发病风险增加有关。粪便β-丙氨酸可能是连接儿童哮喘中肠道微生物群代谢失调、梭菌属和大肠杆菌属的特异性生物标志物。
