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. 2025 Apr 4:15:1537726.
doi: 10.3389/fcimb.2025.1537726. eCollection 2025.

Plasma nontargeted metabolomics study of H1N1 and H3N2 influenza in children

Yaping Li #  1 , Jiaxin Li #  2   3 , Ting Li #  1 , Chenrui Liu  1 , Jiayi Du  4 , Yuxin Li  2 , Yuan Chen  5 , Yufeng Zhang  2 , Xiaoyan Wang  2 , Xinyu Wang  1 , Xiaoli Jia  1 , Huiling Deng  2   6
Affiliations

Plasma nontargeted metabolomics study of H1N1 and H3N2 influenza in children

Yaping Li et al. Front Cell Infect Microbiol. .

Abstract

Background: This study used a nontargeted metabolomic approach to investigate small molecular metabolites in the peripheral blood of pediatric patients with influenza. By comparing these metabolites with those in healthy children, potential biomarkers for the early detection and diagnosis of influenza were explored.

Methods: Plasma samples were collected from 47 children with H1N1 influenza, 40 with H3N2 influenza, and 40 healthy controls at Xi'an Children's Hospital, Xi'an Jiaotong University Second Affiliated Hospital, and Xi'an Central Hospital between May and September 2023. Nontargeted metabolomic detection and analysis were performed.

Results: In the H1N1 group, 14 glycerophospholipid metabolites were significantly altered compared to controls, with 11 (78.5%) markedly downregulated. These downregulated metabolites showed negative correlations with inflammatory markers, including white blood cell (WBC) count, neutrophils, C-reactive protein (CRP), and Procalcitonin (PCT), whereas the upregulated metabolite PC(P-18:1(9Z)/16:0) showed positive correlations with validation markers. In the H3N2 group, 12 glycerophospholipid metabolites were significantly altered, with 9 being downregulated. The downregulated LysoPC(20:0/0:0) showed a positive correlation with alanine aminotransferase (ALT) but a negative correlation with WBC count, while the upregulated metabolite LysoPA(18:1(9Z)0:0) correlated positively with ALT, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH).

Conclusions: Distinct metabolomic profiles were identified in pediatric H1N1 and H3N2 influenza cases compared to healthy controls. Specific glycerophospholipid metabolites were closely associated with inflammatory and liver function markers, highlighting their potential as biomarkers for disease monitoring and early diagnosis.

Keywords: biomarker; differentially abundant metabolites; early diagnosis; influenza virus; plasma metabolomics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Metabolomic analysis of patients in the H1N1 group. OPLS-DA score diagram of pediatric H1N1 influenza patients and healthy controls (A, B);Volcano plot of differential metabolites between children with H1N1 influenza and the healthy control group (C); Top 20 metabolites with the highest VIP values (D); Heatmap of the top 30 different metabolites between children with H1N1 influenza and healthy controls (E); Enrichment analysis of the differentially abundant metabolite pathways in the H1N1 group vs. healthy controls (F).
Figure 2
Figure 2
Metabolomic analysis of patients in the H3N2 group. OPLS-DA score diagram of pediatric H3N2 influenza patients and healthy controls (A, B); Volcano plot of differential metabolites between children with H3N2 influenza and the healthy control group (C); Top 20 metabolites with the highest VIP values (D); Heatmap of the top 30 different metabolites between children with H3N2 influenza and healthy controls (E); Enrichment analysis of the differentially abundant metabolite pathways in the H3N2 group vs. healthy controls (F).
Figure 3
Figure 3
Association between differential glycerophospholipid metabolites and clinical indicators in children with influenza. Association between differential glycerophospholipid metabolites and clinical indicators in children the H1N1 patient and healthy control groups (A); Association between differential glycerophospholipid metabolites and clinical indicators in children the H3N2 patient and healthy control groups (B). * p < 0.05.
Figure 4
Figure 4
Metabolomic analysis of severe and mild groups of influenza patients. OPLS-DA Score Plot of Metabolites in Severe and Mild Cases of H1N1 Influenza infected Children (A, B); Analysis of differential metabolites between H1N1 severe and mild pediatric patients (t-test) (C); Volcano plot of differential metabolites between severe group and mild group in H1N1 patients (D); OPLS-DA Score Plot of Metabolites in Severe and Mild Cases of H3N2 Influenza infected Children (E, F); Analysis of differential metabolites between H3N2 severe and mild pediatric patients (t-test) (G); Volcano plot of differential metabolites between severe group and mild group in H3N2 patients (H).
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