Cholic Acid as a Potential Mediator in PD Olfactory Dysfunction: Insights from Nasal Microbiome-Metabolite Interactions Research

Recent studies suggest a potential connection between PD's olfactory dysfunction and alterations in the nasal microbiome and metabolome, but comprehensive investigations are still lacking.This study aims to explore the interplay between nasal microbiota, metabolites, and olfactory function in PD, identify potential biomarkers for early diagnosis, and investigate therapeutic targets for olfactory dysfunction in PD.he study found significant differences in nasal microbiota composition and metabolite profiles between PD patients and controls, with correlations to the severity of olfactory dysfunction. Specifically, the relative abundances of Corynebacterium, Dolosigranulum, Muribacter, and Moraxella were elevated in the PD group, while the abundances of Hydrogenophaga, Staphylococcus, Klebsiella, and Bacillus decreased. Metabolomic analysis revealed that cholic acid, octanal, hexadecanol, and phytol were significantly altered in PD patients compared to controls, with cholic acid showing potential as a diagnostic biomarker (AUC > 0.97). In MPTP-induced PD mouse models, cholic acid treatment significantly reduced latencies in detecting buried food pellets, and increased tyrosine hydroxylase (TH)-positive fluorescence intensity in the olfactory bulb and substantia nigra. However, cholic acid did not significantly ameliorate motor symptoms in PD mice, as assessed by the open field test, and did not prevent the loss of TH+ cells in the striatum.