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A multi-omics case–control study identifying oropharyngeal microbiome–metabolite patterns that characterize secondary bacterial pneumonia among influenza patients

Hong Zhang, Ran He, Lei Xu, Hang Zhou, Rong-Bin Yu, Peng Huang

Frontiers in Microbiology, 2026

236 participants

Abstract

Secondary bacterial pneumonia is a severe complication of influenza;howeve the biological determinants that distinguish progression from uncomplicated infection remain poorly understood. We investigated the oropharyngeal microbiome and plasma metabolome as potential discriminators of pneumonia development. In this study, we report a cross-sectional case–control study conducted during the 2022–2023 influenza season to identify and internally validate a microbiome-metabolite profile that characterizes pneumonia cases from uncomplicated influenza. We enrolled 236 consecutive influenza patients from Jiangsu Province, China (October 2023–December 2024): 59 with secondary pneumonia and 177 uncomplicated controls. Oropharyngeal swabs were subjected to 16S rRNA V3-V4 sequencing; plasma metabolomics was performed by UPLC-MS/MS in both ion modes. Seven machine-learning algorithms were compared; Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression was selected because it yielded the highest cross-validated discrimination. Microbial composition distinguished groups, not richness. Pneumonia cases showed enrichment of Synergistota and Bifidobacteriaceae with depletion of Bacillaceae (β-diversity p = 0.057). Controls exhibited enriched glycolysis and lipid metabolism pathways; pneumonia cases showed elevated degradation pathways (GLUCARDEG and GALLATE-DEGRADATION). Plasma metabolomics revealed a lipid depletion signature: phospholipids PC(O-16:0/0:0) and…

How strong is the evidence?

Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 236 participants or records.

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