RANK (receptor activator of nuclear factor-kappaB) and RANKL expression in multiple myeloma.

BACKGROUND

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory condition often classified into eosinophilic (Eos) and non-eosinophilic (nonEos) subtypes. While microbial dysbiosis and metabolic disturbance are known contributors to CRSwNP, the interplay between sinonasal microbiota and local metabolic activity remains unclear.

METHODS

We conducted 16S rRNA gene sequencing and untargeted metabolomics on sinonasal swabs and tissue samples from patients with Eos-CRSwNP (n = 14), nonEos CRSwNP (n = 7), and healthy controls (n = 14). Microbial diversity, taxonomic differences, and metabolic alterations were analyzed. Spearman correlation and network modeling were used to explore phenotype-specific microbiotaâ€"metabolite interactions and pathway enrichment.

RESULTS

Eos CRSwNP was characterized by reduced microbial diversity and increased abundance of Staphylococcus and Corynebacterium, along with elevated levels of fumaric acid, linoleic acid, and arachidonic acidâ€"metabolites linked to oxidative stress and lipid-mediated inflammation. In contrast, nonEos-CRSwNP exhibited greater microbial richness, with enrichment of Streptococcus, Anaerococcus, and Clostridium XlVa, and metabolic shifts in amino acid and nitrogen metabolism, including increased glutamine, taurine, and ethanolamine phosphate. Correlation analysis revealed phenotype-specific networks connecting core microbial genera and metabolites, suggesting distinct inflammatory microenvironments between subtypes.

CONCLUSION

Our integrated multi-omics analysis highlights divergent microbial and metabolic signatures in Eos and nonEos CRSwNP. These findings offer mechanistic insights into subtype-specific disease processes and may guide the future development of targeted diagnostic and therapeutic strategies.