Education as risk factor of Mild Cognitive Impairment - the role of the gut microbiome

Poster (2023, July)

The gut microbiome molecular complex in human health and disease

in Cell Host and Microbe (2022), 30(9), 1201-1206

The human gut microbiome produces a functional complex of biomolecules, including nucleic acids, (poly) peptides, structural molecules, and metabolites. This impacts human physiology in multiple ways ... [more ▼]

The human gut microbiome produces a functional complex of biomolecules, including nucleic acids, (poly) peptides, structural molecules, and metabolites. This impacts human physiology in multiple ways, especially by triggering inflammatory pathways in disease. At present, much remains to be learned about the identity of key effectors and their causal roles. [less ▲]

Studying the Parkinson's disease metabolome and exposome in biological samples through different analytical and cheminformatics approaches: a pilot study

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 ▲]

Gut microbiome signatures of risk and prodromal markers of Parkinson's disease

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 ▲]

Gut microbiota in Parkinson's disease: Temporal stability and relations to disease progression

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 ▲]

Gut microbiome in gestational diabetes: a cross-sectional study of mothers and offspring 5 years postpartum

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

Skin microbiome in small- and large-plaque parapsoriasis

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

More than constipation – bowel symptoms in Parkinson's disease and their connection to gut microbiota

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

Skin microbiome in melanomas and melanocytic nevi

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

Gut microbiota are related to Parkinson's disease and clinical phenotype

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