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See detailStudying the Parkinson's disease metabolome and exposome in biological samples through different analytical and cheminformatics approaches: a pilot study
Talavera Andujar, Begona UL; Aurich, Dagny UL; Aho, Velma UL et al

in Analytical and Bioanalytical Chemistry (2022)

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, with an increasing incidence in recent years due to the ageing population. Genetic mutations alone only explain <10% of PD ... [more ▼]

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, with an increasing incidence in recent years due to the ageing population. Genetic mutations alone only explain <10% of PD cases, while environmental factors, including small molecules, may play a significant role in PD. In the present work, 22 plasma (11 PD, 11 control) and 19 feces samples (10 PD, 9 control) were analyzed by non-target high resolution mass spectrometry (NT-HRMS) coupled to two liquid chromatography (LC) methods (reversed phase (RP) and hydrophilic interaction liquid chromatography (HILIC)). A cheminformatics workflow was optimized using open software (MS-DIAL and patRoon) and open databases (all public MSP-formatted spectral libraries for MS-DIAL, PubChemLite for Exposomics and the LITMINEDNEURO list for patRoon). Furthermore, five disease-specific databases and three suspect lists (on PD and related disorders) were developed, using PubChem functionality to identifying relevant unknown chemicals. The results showed that non-target screening with the larger databases generally provided better results compared with smaller suspect lists. However, two suspect screening approaches with patRoon were also good options to study specific chemicals in PD. The combination of chromatographic methods (RP and HILIC) as well as two ionization modes (positive and negative) enhanced the coverage of chemicals in the biological samples. While most metabolomics studies in PD have focused on blood and cerebrospinal fluid, we found a higher number of relevant features in feces, such as alanine betaine or nicotinamide, which can be directly metabolized by gut microbiota. This highlights the potential role of gut dysbiosis in PD development. [less ▲]

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See detailAn archaeal compound as a driver of Parkinson’s disease pathogenesis
Trezzi, Jean-Pierre; Aho, Velma UL; Jäger, Christian UL et al

E-print/Working paper (2022)

Patients with Parkinson’s disease (PD) exhibit differences in their gut microbiomes compared to healthy individuals. Although differences have most commonly been described in the abundances of bacterial ... [more ▼]

Patients with Parkinson’s disease (PD) exhibit differences in their gut microbiomes compared to healthy individuals. Although differences have most commonly been described in the abundances of bacterial taxa, changes to viral and archaeal populations have also been observed. Mechanistic links between gut microbes and PD pathogenesis remain elusive but could involve molecules that promote α-synuclein aggregation. Here, we show that 2-hydroxypyridine (2-HP) represents a key molecule for the pathogenesis of PD. We observe significantly elevated 2-HP levels in faecal samples from patients with PD or its prodrome, idiopathic REM sleep behaviour disorder (iRBD), compared to healthy controls. 2-HP is correlated with the archaeal species Methanobrevibacter smithii and with genes involved in methane metabolism, and it is detectable in isolate cultures of M. smithii. We demonstrate that 2-HP is selectively toxic to transgenic α-synuclein overexpressing yeast and increases α-synuclein aggregation in a yeast model as well as in human induced pluripotent stem cell derived enteric neurons. It also exacerbates PD-related motor symptoms, α-synuclein aggregation, and striatal degeneration when injected intrastriatally in transgenic mice overexpressing human α-synuclein. Our results highlight the effect of an archaeal molecule in relation to the gut-brain axis, which is critical for the diagnosis, prognosis, and treatment of PD. [less ▲]

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See detailGut microbiome signatures of risk and prodromal markers of Parkinson's disease
Heinzel, Sebastian; Aho, Velma UL; Suenkel, Ulrike et al

in Annals of Neurology (2020)

Objective: Alterations of the gut microbiome in Parkinson disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they relate ... [more ▼]

Objective: Alterations of the gut microbiome in Parkinson disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they relate to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition. Methods: Established risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function, and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and differential abundance in stool samples of 666 elderly TREND (Tübingen Evaluation of Risk Factors for Early Detection of Neurodegeneration) study participants. Results: Among risk and prodromal markers, physical activity, occupational solvent exposure, and constipation showed associations with α-diversity. Physical activity, sex, constipation, possible rapid eye movement sleep behavior disorder (RBD), and smoking were associated with β-diversity. Subthreshold parkinsonism and physical activity showed an interaction effect. Among other factors, age and urate-lowering medication were associated with α- and β-diversity. Physical inactivity and constipation were highest in individuals with the Firmicutes-enriched enterotype. Constipation was lowest and subthreshold parkinsonism least frequent in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical activity, possible RBD, smoking, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history, and the prodromal PD probability showed no significant microbiome associations. Interpretation: Several risk and prodromal markers of PD are associated with gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases. [less ▲]

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See detailIncreasing comparability and utility of gut microbiome studies in Parkinson's disease: A systematic review
Boertien, J. M.; Pereira, P. A. B.; Aho, Velma UL et al

in Journal of Parkinson's Disease (2019), 9(s2), 297-312

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See detailGut microbiota in Parkinson's disease: Temporal stability and relations to disease progression
Aho, Velma UL; Pereira, P. A. B.; Voutilainen, S. et al

in EBioMedicine (2019), 44

Background: Several publications have described differences in cross-sectional comparisons of gut microbiota between patients with Parkinson's disease and control subjects, with considerable variability ... [more ▼]

Background: Several publications have described differences in cross-sectional comparisons of gut microbiota between patients with Parkinson's disease and control subjects, with considerable variability of the reported dif- ferentially abundant taxa. The temporal stability of such microbiota alterations and their relationship to disease progression have not been previously studied with a high-throughput sequencing based approach. Methods: We collected clinical data and stool samples from 64 Parkinson's patients and 64 control subjects twice, on average 2·25 years apart. Disease progression was evaluated based on changes in Unified Parkinson's Disease Rating Scale and Levodopa Equivalent Dose, and microbiota were characterized with 16S rRNA gene amplicon sequencing. Findings: We compared patients to controls, and patients with stable disease to those with faster progression. There were significant differences between microbial communities of patients and controls when corrected for confounders, but not between timepoints. Specific bacterial taxa that differed between patients and controls at both timepoints included several previously reported ones, such as Roseburia, Prevotella and Bifidobacterium. In progression comparisons, differentially abundant taxa were inconsistent across methods and timepoints, but there was some support for a different distribution of enterotypes and a decreased abundance of Prevotella in faster-progressing patients. Interpretation: The previously detected gut microbiota differences between Parkinson's patients and controls persisted after 2 years. While we found some evidence for a connection between microbiota and disease progres- sion, a longer follow-up period is required to confirm these findings. [less ▲]

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See detailIsotretinoin and lymecycline treatments modify the skin microbiota in acne
Kelhälä, H.-L.; Aho, Velma UL; Fyhrquist, N. et al

in Experimental Dermatology (2018), 27(1), 30-36

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See detailGut microbiome in gestational diabetes: a cross-sectional study of mothers and offspring 5 years postpartum
Hasan, S.; Aho, Velma UL; Pereira, P. A. B. et al

in Acta Obstetricia et Gynecologica Scandinavica (2018), 97(1), 38-46

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See detailOral and nasal microbiota in Parkinson's disease
Pereira, P. A. B.; Aho, Velma UL; Paulin, L. et al

in Parkinsonism and Related Disorders (2017), 38

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See detailSkin microbiome in small- and large-plaque parapsoriasis
Salava, A.; Pereira, P.; Aho, Velma UL et al

in Acta Dermato Venereologica (2017), 97(6), 685-691

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See detailLoss of cutaneous microbial diversity during first 3 weeks of life in very low birthweight infants
Salava, A.; Aho, Velma UL; Lybeck, E. et al

in Experimental Dermatology (2017), 26(10), 861-867

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See detailMore than constipation – bowel symptoms in Parkinson's disease and their connection to gut microbiota
Mertsalmi, T. H.; Aho, Velma UL; Pereira, P. A. B. et al

in European Journal of Neurology (2017), 24(11), 1375-1383

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See detailBile microbiota in primary sclerosing cholangitis: Impact on disease progression and development of biliary dysplasia
Pereira, P.; Aho, Velma UL; Arola, J. et al

in PLoS ONE (2017), 12(8), 0182924

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See detailSkin microbiome in melanomas and melanocytic nevi
Salava, A.; Aho, Velma UL; Pereira, P. et al

in European Journal of Dermatology (2016), 26(1), 49-55

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See detailThe microbiome of the human lower airways: a next generation sequencing perspective
Aho, Velma UL; Pereira, P. A. B.; Haahtela, T. et al

in World Allergy Organization Journal (2015), 8(1), 23-015-0074-

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See detailGut microbiota are related to Parkinson's disease and clinical phenotype
Scheperjans, F.; Aho, Velma UL; Pereira, P. A. B. et al

in Movement Disorders (2015), 30(3), 350-358

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