Gut microbiota and serum metabolome in children with human metapneumovirus infection.

Objective: To analyze the alterations in gut microbiota structure and serum metabolic profiles of children with human metapneumovirus (hMPV) infection using 16S rRNA high-throughput sequencing and liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics. Through integrated multi-omics analysis, we aim to explore the correlation between gut microbiota dysbiosis and host metabolic disorder, provide preliminary evidence for potential intervention targets, and offer primary clues for the development of preventive and therapeutic strategies including probiotic supplementation and metabolic pathway regulation. Methods: This study enrolled 42 children with hMPV infection and 12 healthy controls. Fecal samples were collected for gut microbiota analysis using 16S rRNA gene sequencing, and serum samples were obtained for metabolomic profiling via LC-MS. Various bioinformatics approaches were applied for independent analysis of microbiome and metabolome data, followed by integrated multi-omics analysis. Results: The microbial community structure of the hMPV-infected group was clearly separated from that of the healthy control group. Opportunistic pathogens such as Finegoldia, Anaerococcus, and Peptoniphilus were enriched, while beneficial commensals including Bifidobacterium, Blautia, and Faecalibacterium were reduced. Serum metabolic profiles showed global divergence between the two groups, with 558 upregulated and 213 downregulated metabolites identified. Using a VIP threshold >1.5, 24 core differential metabolites were ultimately selected. KEGG enrichment and MetPA topological analyses revealed that these differential metabolites were mainly enriched in pathways including glycerophospholipid metabolism, nucleotide metabolism, alpha-linolenic acid metabolism, and arachidonic acid metabolism. Correlation analysis showed that beneficial commensals with reduced abundance in the infected group, such as Bifidobacterium and Blautia, were positively correlated with anti-inflammatory and barrier-protective metabolites (e.g., alpha-linolenic acid, 11,12-DiHETrE, GPCho(20:4/14:0)), and negatively correlated with pro-inflammatory lipid mediators (e.g., 12,13-DiHOME, 9-OxoODE, vernolic acid). Conclusion: This study indicated that hMPV infection might be associated with intestinal microecological imbalance and serum metabolic disturbances in children. The screened core differential metabolites hold the potential for further evaluation of their diagnostic value. Significant correlations exist between gut microbiota alterations and serum metabolic disorders, providing preliminary clues for the future development of preventive and therapeutic strategies targeting gut microbiota or metabolic pathways.