Reduced olfactory performance is associated with changed microbial diversity, oralization, and accumulation of dead...

The partial or complete loss of the sense of smell, which affects about 20% of the population, impairs the quality of life in many ways. Dysosmia and anosmia are mainly caused by aging, trauma, infections, or even neurodegenerative disease. Recently, the olfactory area-a site containing the olfactory receptor cells responsible for odor perception-was shown to harbor a complex microbiome that reflects the state of olfactory function. This initially observed correlation between microbiome composition and olfactory performance needed to be confirmed using a larger study cohort and additional analyses. A total of 120 participants (middle-aged, no neurodegenerative disease) were enrolled in the study to further analyze the microbial role in human olfactory function. Olfactory performance was assessed using the Sniffin' Stick battery, and participants were grouped accordingly (normosmia: n = 93, dysosmia: n = 27). The olfactory microbiome was analyzed by 16S rRNA gene amplicon sequencing and supplemented by metatranscriptomics in a subset (Nose 2.0). Propidium monoazide (PMA) treatment was performed to distinguish between intact and non-intact microbiome components. The gastrointestinal microbiome of these participants was also characterized by amplicon sequencing and metabolomics and then correlated with food intake. Our results confirm that normosmics and dysosmics indeed possess a distinguishable olfactory microbiome. Alpha diversity (i.e., richness) was significantly increased in dysosmics, reflected by an increase in the number of specific taxa (e.g., Rickettsia, Spiroplasma, and Brachybacterium). Lower olfactory performance was associated with microbial signatures from the oral cavity and periodontitis (Fusobacterium, Porphyromonas, and Selenomonas). However, PMA treatment revealed a higher accumulation of dead microbial material in dysosmic subjects. The gastrointestinal microbiome partially overlapped with the nasal microbiome but did not show substantial variation with respect to olfactory performance, although the diet of dysosmic individuals was shifted toward a higher meat intake. Dysosmia is associated with a higher burden of dead microbial material in the olfactory area, indicating an impaired clearance mechanism. As the microbial community of dysosmics (hyposmics and anosmics) appears to be influenced by the oral microbiome, further studies should investigate the microbial oral-nasal interplay in individuals with partial or complete olfactory loss.IMPORTANCEThe loss of the sense of smell is an incisive event that is becoming increasingly common in today's world due to infections such as COVID-19. Although this loss usually recovers a few weeks after infection, in some cases, it becomes permanent-why is yet to be answered. Since this condition often represents a psychological burden in the long term, there is a need for therapeutic approaches. However, treatment options are limited or even not existing. Understanding the role of the microbiome in the impairment of olfaction may enable the prediction of olfactory disorders and/or could serve as a possible target for therapeutic interventions.