Microbiota and Mycobiota Dysbiosis in Sinonasal Fungus Ball

Objective(s): Fungus ball (FB) is a unilateral form of fungal rhinosinusitis, but it remains unclear whether associated microbial dysbiosis is restricted to the lesional sinus or extends across the sinonasal cavity. This study aimed to determine whether bacterial and fungal dysbiosis in maxillary sinus FB is spatially localized by comparing paired lesional and contralateral-normal sites within the same individuals. Methods: This prospective paired-sample study enrolled 14 adults with surgically confirmed unilateral maxillary sinus FB at a tertiary referral center. Middle-meatal swabs were obtained from lesional and contralateral-normal sides during endoscopic sinus surgery. Bacterial and fungal communities were profiled using 16S rRNA gene and internal transcribed spacer (ITS) sequencing. Alpha and beta diversity, taxonomic composition, predicted functional pathways, and bacterial–fungal co-occurrence networks were analyzed. Results: Lesional sinuses showed significantly reduced bacterial alpha diversity compared with contralateral-normal sides (Wilcoxon p < 0.001) and distinct bacterial beta diversity (PERMANOVA p = 0.003). Fungal beta diversity also differed between sites (p = 0.001), whereas fungal alpha diversity was preserved. Lesional communities showed enrichment of anaerobic and pathobiont taxa, including Haemophilus, Enterococcus, and Pseudomonas, with reduced relative abundance of Staphylococcus. Although Aspergillus abundance was similar bilaterally, network analysis suggested altered Aspergillus-associated connectivity in lesional samples, consistent with a shift in inferred interaction topology rather than increased Aspergillus abundance. Predicted functional analysis further suggested pathway differences that may reflect altered local metabolic conditions. Conclusion: In this cohort, microbial dysbiosis in maxillary sinus FB appeared to be spatially localized, with patterns suggestive of anaerobe enrichment and ecological reorganization centered on Aspergillus. These findings are compatible with the standard surgical emphasis on fungal mass removal and restoration of sinus drainage/aeration, but the microbiome-based relevance of aeration requires confirmation in larger studies. Level of Evidence: 3.