Disease-modifying therapies are associated with improved olfactory function via NK cell- microbiota interactions in multiple sclerosis

Objective To examine the associations of nasal microbiota with disease-modifying therapies (DMTs), lymphocyte subsets and olfactory function in multiple sclerosis (MS). Methods Thirty patients with MS and 30 age- and sex-matched healthy controls (HCs) were enrolled. Patients were classified as DMT-treated (MS[DMT+]) or untreated (MS[DMT-]). Olfactory function was assessed using the University of Pennsylvania Smell Identification Test (UPSIT). Lymphocyte subsets were measured by flow cytometry, and nasal microbiota were analysed by 16S rRNA sequencing. Results Olfactory function was lower in MS than in HCs, and better in MS(DMTs+) than in MS(DMTs−) ( p =0.016, 95% CI 0.5614 to 4.941). NK cell counts were lower in MS(DMTs+) than in MS(DMTs−) ( p =0.049, 95% CI -244.7 to -0.2109). And NK cell counts in MS(DMTs+) correlate with UPSIT ( r =-0.527, p =0.029). Compared with HCs, MS(DMTs−) showed higher Shannon diversity ( p =0.038), increased Proteobacteria ( p =0.004), reduced Moraxellaceae ( p =0.037) and Enterobacteriaceae ( p =0.033), and enriched branched-chain amino acid biosynthesis ( p =0.026). In MS(DMTs+), Campylobacter, Anaerococcus, Peptoniphilus, Prevotella , and Finegoldia were positively correlated with circulating NK cells (all p <0.05). Conclusion DMTs may improve olfactory function in MS, possibly through modulation of circulating NK cell-associated immune status and nasal microbiota, in addition to controlling disease-related inflammation.