Chao Jia, 1, Xiaoge Liu, 2, 3, Wenjing Liu, 2 Xingfeng Yao, 1 Xiaoxu Chen, 2 Jinhao Zhao, 2 Pengpeng Wang, 2 Wentong Ge, 2, 4, 5 Yang Han2 1Department of Pathology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 2Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 3The Sixth Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 4Beijing City Key Laboratory of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 5Department of Otolaryngology, Head and Neck Surgery, National Clinical Research Center for Respiratory Diseases, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of ChinaThese authors contributed equally to this workCorrespondence: Wentong Ge, Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 56 NanLishi Road, Xicheng District, Beijing, 100045, People’s Republic of China, Tel +86 010-5961 6391, Email gwt@bch. com. cn Yang Han, Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 56 NanLishi Road, Xicheng District, Beijing, 100045, People’s Republic of China, Tel +86 010-5961 6391, Email hanyₑnt@126. comBackground: Chronic rhinosinusitis with nasal polyps (CRSwNP) in children is a clinically significant inflammatory disorder characterized by persistent symptoms and complex underlying mechanisms. This study used multi-omics approaches to investigate potential microbial and metabolic associations in pediatric CRSwNP. Methods: Nasal secretions from 20 children with CRSwNP and 19 healthy controls were analyzed using metagenomics, untargeted metabolomics, and proteomics. Results: CRSwNP patients showed higher microbial diversity and altered microbial communities, with increased Streptococcus abundance. Metabolomic sequencing revealed that 13′-Hydroxy-alpha-tocopherol was significantly upregulated in the CRSwNP group and exhibited a positive correlation with the abundance of Streptococcus. Proteomic sequencing revealed that proteins involved in glutathione metabolism were significantly downregulated in the CRSwNP group, with GCLM and GGCT showing a significant negative correlation with 13′-Hydroxy-alpha-tocopherol. Conclusion: These associative findings suggest potential links among Streptococcus, 13′-Hydroxy-α-tocopherol, and glutathione metabolism, indicating that oxidative stress–related imbalance may contribute to pediatric CRSwNP. These results provide preliminary evidence that 13′-Hydroxy-α-tocopherol may serve as a potential biomarker for pediatric CRSwNP. Keywords: chronic rhinosinusitis with nasal polyps, streptococcus, 13′-hydroxy-alpha-tocopherol, glutathione metabolism, multi-omics
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