Gut Microbiome and Metabolomics Profiles of Allergic and Non-Allergic Childhood Asthma

Ping Zheng,1 Kexing Zhang,2 Xifang Lv,1 Chuanhe Liu,3 Qiang Wang,1 Xuetao Bai1 1China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Immunization Program, Xinwu District Center for Disease Control and Prevention, Wuxi, People’s Republic of China; 3Children’s Hospital, Capital Institute of Pediatrics, Beijing, People’s Republic of ChinaCorrespondence: Qiang Wang; Xuetao Bai, China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +86 10 50930251, Email wangqiang@nieh.chinacdc.cn; xuetaobai@163.comPurpose: This study aimed to investigate the characteristics of gut bacteria and the derived metabolites among allergic asthmatic children, non-allergic asthmatic children and healthy children without asthma.Methods: Fecal samples were collected from 57 participants, including 20 healthy children, 27 allergic asthmatic children, and 10 non-allergic asthmatic children. 16S rRNA gene sequencing was conducted for analyzing gut bacterial compositions and untargeted metabolomics was used to analyze the alterations of gut microbe-derived metabolites. The associations between gut bacterial compositions and metabolites were analyzed by the method of Spearman correlation.Results: The results showed that the compositions and metabolites of gut microbiome were altered both in allergic and non-allergic asthmatics compared with healthy controls. Chao1 (p = 0.025) index reflected a higher bacterial richness and Simpson (p = 0.024) index showed a lower diversity in asthma group. PERMANOVA analysis showed significant differences among the three groups based on unweighted UniFrac distance (p = 0.001). Both allergic and non-allergic asthmatics showed a higher relative abundance of Proteobacteria and a lower relative abundance of genera from Clostridia. More bacteria were altered in non-allergic asthmatics compared with allergic asthmatics. Metabolomics analysis identified that 42 metabolites were significantly associated with allergic asthma, and 58 metabolites were significantly associated with non-allergic asthma (multiple linear regression, p < 0.05). Histamine was 4 folds up-regulated only in the non-allergic asthma group. The relative abundance of Candidatus Accumulib was significantly correlated with the upregulation of histamine. The relative abundance of genera from Clostridia was significantly correlated with the downregulation of lipid and tryptophan metabolism.Conclusion: The altered gut microbes was associated with the mechanism of asthma attack through metabolites in allergic and non-allergic asthma group, respectively. The result suggested that gut microbiome had an impact on the development of both allergic and non-allergic asthma. The distinct gut microbiome and microbiome-derived metabolites in non-allergic asthma children suggested that gut microbiome might play a critical role in modulation of asthma phenotype.Keywords: gut microbiome, untargeted metabolomics, allergic childhood asthma, non-allergic childhood asthma, 16S rRNA gene sequencing