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ABSTRACT:
PROVIDER: PRJNA1287375 | ENA |
REPOSITORIES: ENA
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Project description:<p>Background: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by both motor and non-motor symptoms, including olfactory dysfunction, which often precedes motor symptoms by several years. However, the underlying mechanisms linking olfactory dysfunction in PD to biological changes remain unclear. 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.</p><p> </p><p>Methods: From October 1, 2023, to September 30, 2024, 66 potential participants were enrolled, including PD patients with varying degrees of olfactory dysfunction and healthy controls. Nasal samples were collected for 16S rRNA sequencing and metabolomic analysis using GC-MS. The study also used MPTP-induced PD mouse models to assess the protective effects of cholic acid on olfactory function and dopaminergic neurons.</p><p> </p><p>Results: The 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.</p><p> </p><p>Conclusion: The findings highlight the interplay between the nasal microbiome, metabolome, and olfactory dysfunction in PD, suggesting that modulating metabolic pathways could be a promising therapeutic strategy. Future research should focus on larger sample sizes, longitudinal studies, and further validation of biomarkers and therapeutic targets to enhance the understanding and management of PD.</p>
2025-07-07 | MTBLS12692 | MetaboLights
Project description:Olfactory dysfunction is one of the earliest features in Lewy-type alpha-synucleinopathies (LTS) such as Parkinson´s disease (PD). However, the underlying molecular mechanisms associated to smell impairment is poorly understood. To reveal the missing links in the biochemical understanding of olfactory dysfunction in PD, we have applied mass spectrometry-based proteomics in postmortem olfactory bulbs (OBs) dissected from parkinsonian subjects with different LTS staging respect to elderly controls (n= 24, mean age 79 years).
2018-10-24 | PXD008036 | Pride
Project description:<p><strong>PURPOSE:</strong> Olfactory dysfunction (OD) is a debilitating symptom frequently reported by patients with chronic rhinosinusitis (CRS) and it is associated with a dysregulated sinonasal inflammation. However, little information is available about the effect of the inflammation-related nasal microbiota and related metabolites on the olfactory function in these patients. Therefore, the current study aimed to investigate the nasal microbiota-metabolites-immune interactions and their role in the pathogenesis of OD in CRS patients.</p><p><strong>METHODS:</strong> 23 and 19 CRS patients with and without OD (NOD), respectively, were enrolled in the present study. The 'Sniffin' Sticks' was used to measure the olfactory function, while the metagenomic shotgun sequencing and the untargeted metabolomic profiling were performed to assess the differences in terms of the nasal microbiome and metabolome between the two groups. The levels of nasal mucus inflammatory mediators were investigated by a multiplex flow Cytometric Bead Array (CBA).</p><p><strong>RESULTS:</strong> A decreased diversity in the nasal microbiome from the OD group compared to the NOD group was evidenced. The metagenomic analysis revealed a significant enrichment of <em>Acinetobacter johnsonii</em> in the OD group, while <em>Mycoplasma arginini</em>, <em>Aeromonas dhakensis</em> and <em>Salmonella enterica</em> were significantly less represented (LDA value > 3, p < 0.05). The nasal metabolome profiles were significantly different between the OD and NOD groups (P < 0.05). The purine metabolism was the most significantly enriched metabolic subpathway in OD patients compared with NOD patients (P < 0.001). The expressions of IL-5, IL-8, MIP-1alpha, MCP-1 and TNF were statistically and significantly increased in the OD group (P < 0.05). All these data, including the dysregulation of the nasal microbiota, differential metabolites and elevated inflammatory mediators in OD patients demonstrated a clear interaction relationship.</p><p><strong>CONCLUSIONS:</strong> The disturbed nasal microbiota-metabolite-immune interaction networks may be implicated in the pathogenesis of OD in CRS patients and the underlying pathophysiological mechanisms need to be further investigated in future studies.</p>
2023-05-12 | MTBLS7584 | MetaboLights
Project description:SARS-CoV-2 infects the nasal epithelium (NE) and can cause olfactory dysfunction. Because the virus cannot infect olfactory sensory neurons (OSNs) which detect odorants, the underlying mechanisms remain unknown. Here, using human embryonic stem cells, we were the first to develop human NE organoids comprising both olfactory neuroepithelia (OE) and nasal respiratory epithelia (NRE). SARS-CoV-2 initially replicated in the NRE and then spread to the OE where angiotensin converting enzyme 2 was expressed after virus replication in NRE. Importantly, a significant proportion of neural precursor cells (NPCs) and basal stem cells in the OE, both of which constantly differentiate into OSNs, were infected. Viral infection upregulated cell death-associated genes in the NPCs and basal stem cells, suggesting that SARS-CoV-2 infection disrupts the repair and renewal of OSNs. Taken together, our human nasal organoid model would be useful for the investigation of a potential mechanism underlying olfactory dysfunction in COVID-19 patients.
2025-10-06 | GSE309325 | GEO
Project description:Parkinson’s disease (PD) is characterized by multiple symptoms including olfactory dysfunction, whose underlying mechanisms remain unclear. Here, we explored pathologic changes in the olfactory pathway of transgenic (Tg) mice of both sexes expressing the human A30P mutant α-synuclein (α-syn; α-syn-Tg mice) at 6–7 and 12–14 months of age, representing early and late-stages of motor progression, respectively. α-Syn-Tg mice at late stages exhibited olfactory behavioral deficits, which correlated with severe α-syn pathology in projection neurons (PNs) of the olfactory pathway. In parallel, olfactory bulb (OB) neurogenesis in α-syn-Tg mice was reduced in the OB granule cells at six to seven months and OB periglomerular cells at 12–14 months, respectively, both of which could contribute to olfactory dysfunction. Proteomic analyses showed a disruption in endocytic and exocytic pathways in the OB during the early stages which appeared exacerbated at the synaptic terminals when the mice developed olfactory deficits at 12–14 months. Our data suggest that (1) the α-syn-Tg mice recapitulate the olfactory functional deficits seen in PD; (2) olfactory structures exhibit spatiotemporal disparities for vulnerability to α-syn pathology; (3) α-syn pathology is restricted to projection neurons in the olfactory pathway; (4) neurogenesis in adult α-syn-Tg mice is reduced in the OB; and (5) synaptic endocytosis and exocytosis defects in the OB may further explain olfactory deficits.
2023-01-13 | PXD039396 | Pride
Project description:Chronic rhinitis (CR) is a frustrating clinical syndrome in dogs and our understanding of the disease pathogenesis in is limited. Increasingly, host-microbe interactions are considered key drivers of clinical disease in sites of persistent mucosal inflammation such as the nasal and oral cavities. Therefore, we applied next generation sequencing tools to interrogate abnormalities present in the nose of dogs with CR and compared immune and microbiome profiles to those of healthy dogs. Host nasal cell transcriptomes were evaluated by RNA sequencing, while microbial communities were assessed by 16S rRNA sequencing. Correlation analysis was then used to identify significant interactions between nasal cell transcriptomes and the nasal microbiome and how these interactions were altered in animals with CR. Notably, we observed significant downregulation of multiple genes associated with ciliary function in dogs with CR, suggesting a previously undetected role for ciliary dysfunction in this syndrome. We also found significant upregulation of immune genes related to the TNF-a and interferon pathways. The nasal microbiome was also significantly altered in CR dogs, with overrepresentation of several potential pathobionts. Interactome analysis revealed significant correlations between bacteria in the genus Porphyromonas and the upregulated host inflammatory responses in dogs with CR, as well as defective ciliary function which was correlated with Streptococcus abundance. These findings provide new insights into host-microbe interactions in a canine model of CR and indicate the presence of potentially causal relationships between nasal pathobionts and the development of nasal inflammation and ciliary dysfunction.
2024-08-08 | GSE255529 | GEO
Project description:Nasal mucosa and olfactory bulb are separated by the cribriform plate which is perforated by olfactory nerves. We have previously demonstrated that the cribriform plate is permissive for T cells and monocytes and that viruses can enter the bulb upon intranasal injection by axonal transportation. Therefore, we hypothesized that nasal mucosa and olfactory bulb are equipped to deal with constant infectious threats. To detect genes involved in this process, we compared gene expression in nasal mucosa and bulb of mice kept under specific pathogen free (SPF) conditions to gene expression of mice kept on non-SPF conditions using RNA deep sequencing. We found massive alterations in the expression of immune-related genes of the nasal mucosa, while the bulb did not respond immunologically. The absence of induction of immune-related genes in the olfactory bulb suggests effective defence mechanisms hindering entrance of environmental pathogens beyond the outer arachnoid layer. The genes detected in this study may include candidates conferring susceptibility to meningitis.
2018-02-13 | GSE102457 | GEO
Project description:Unilateral naris occlusion was performed the day after birth in three FVB strain mice. At 25 days of age olfactory mucosa was collected from open nasal fossa, the occluded nasal fossa and from three untreated mice. Total RNA was extracted and gene profiles among these three treatment conditions were compared. The goal of the study was to determine the effect of stimulus deprivation on the genetic profile of olfactory mucosa.
2012-08-22 | GSE33833 | GEO
Project description:This study is a double-blinded, randomized, placebo controlled, multi-center trial in which 120 subjects with nasal polyposis (NP) will be treated during 20 days with oral corticosteroids (OCS) in decreasing doses or oral doxycyclin (ODOX) or placebo. At each visit the clinical and the biological activity will be assessed by nasal peak inspiratory flow (nPIF), symptoms, olfactory test, endoscopic evaluation of nasal polyps, peripheral eosinophil levels and markers of inflammation IL-5, IL-5 receptor alpha, ECP, TGFβ1, IgE and specific IgE in serum and nasal secretion.
| 2040498 | ecrin-mdr-crc