Characterizing the nasal metabolome and exposome by LC-HRMS: Opportunities and challenges

ABSTRACT:

The nasal cavity represents a host-microbial interface critical to respiratory defense against viral infections, including those caused by influenza virus, respiratory syncytial virus, rhinovirus or SARS-CoV-2. Although the nasal microbiome itself has been well characterized, the nasal metabolome remains comparatively unexplored. In this proof-of-concept study, we developed and critically evaluated an LC-HRMS based workflow for small molecule analysis in nasal swab samples, focusing on endogenous metabolites and the analytical feasibility of trace-level xenobiotics detection. Nasal swab samples and paired plasma samples were collected from ten volunteers. Samples were processed using different extraction volumes and strategies, including liquid and solid-phase extraction, and analyzed by HILIC- and RP-LC-HRMS in positive and negative ionization modes. Targeted evaluation of the HILIC dataset using authentic reference standards enabled (semi-)quantification of endogenous metabolites in both matrices, suggesting that nasal swab sampling can provide information on the local nasal metabolic environment. Complementary untargeted analysis showed a lower feature yield and annotation coverage in nasal swabs than in plasma. RP-based exposure compound analysis was impacted by a nasal swab-derived PEG-like polymer background, which broadly interfered with the detection of low-abundance xenobiotics. Although a small number of the selected targets were detectable in spiked pooled nasal swab extracts, the overall sensitivity was insufficient to detect them in experimental samples. These findings demonstrate the feasibility of nasal swab-based LC-HRMS metabolomics for endogenous metabolites, whereas exposomic analysis would require further optimization of swab material, cleanup, and enrichment strategies. The presented workflow offers a novel tool for investigating the nasal metabolic landscape.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - hilic, Liquid Chromatography MS - positive - reverse-phase, Liquid Chromatography MS - negative - hilic

PROVIDER: MTBLS14409 | MetaboLights | 2026-10-22

REPOSITORIES: MetaboLights