Microbial and Metabolomic Profiling of the Upper Respiratory Tract in Children with Asthma

Lina Xu¹Qianjun Wan²Quying Yang¹Wenxin Shen¹Yinfang Dai¹Huiquan Sun¹Li Huang¹Meijuan Wang¹Wujun Jiang^1*Chuangli Hao^1*

• ¹Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou, China
• ²Emergency Department, Maternal and Child Health Hospital of Hubei Province, Wuhan, China

Background This study aimed to investigate characteristic changes in the upper respiratory tract (URT) microbiome and metabolome in children with asthma and explore their associations with lung function. Methods Children with asthma aged 6 years and above admitted to the Children's Hospital of Soochow University from December 2022 to December 2023 comprised the study group. Age-matched healthy children undergoing physical examinations in the Department of Child Health were recruited as controls.Throat swabs were collected for microbiome detection using 16S rDNA sequencing and metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS). Results 1. Significant differences in alpha and beta diversity were observed among the control group (H), chronic persistent asthma group (CA), and acute exacerbation group (AA). In both CA and AA groups, FVC% predicted (FVC%/Pred) and FEV1% predicted (FEV1%/Pred) were negatively correlated with URT microbiota community variation as assessed by ordination analysis. Actinobacillus abundance was positively correlated with FEV1%/Pred, FEV1/FVC, FEF25%/Pred, FEF50%/Pred, and FEF75%/Pred. 2. Metabolite differences between CA and AA groups were analyzed, and the top differential metabolites were evaluated for their discriminatory performance between disease states. L-carnitine showed an AUC > 0.9, with a sensitivity of 85.7% and specificity of 85%. Other differential metabolites, including monoisobutyl phthalate, 4-hexyl-2,5-dimethyloxazole, and dibutyl phthalate, correlated with several lung function indices. The most relevant differential metabolic pathways included arginine biosynthesis, alanine-aspartate-glutamate metabolism, central carbon metabolism in cancer, and D-amino acid metabolism. Conclusion The URT microbiota in asthmatic children exhibits alterations in composition, structure, and diversity, with lower diversity in acute asthma compared to chronic persistent asthma. At were negatively correlated with URT microbiota abundance 删除[lina xu]: and the top 5 differential metabolites were evaluated for their accuracy as asthma assessment biomarkers 删除[lina xu]: the genus level, some microbiota (Actinobacillus, Fusobacterium) were correlated with FEV1%/Pred, FEV1/FVC, FEF25%/Pred, FEF50%/Pred, FEF75%/Pred. The differential metabolite L-carnitine was associated with asthma exacerbation status in this cohort and represents a candidate marker that warrants further validation. The differential metabolite L-carnitine may be a potential biomarker for asthma assessment. 删除[lina xu]: