Sebastian Heinzel1, Velma T E Aho2,3, Ulrike Suenkel4, Anna-Katharina von Thaler4, Claudia Schulte4,5, Christian Deuschle4,5, Lars Paulin2, Sari Hantunen6, Kathrin Brockmann4,5, Gerhard W Eschweiler7,8, Walter Maetzler1, Daniela Berg1,4, Petri Auvinen2, Filip Scheperjans3. 1. Department of Neurology, Christian-Albrechts University of Kiel, Kiel, Germany. 2. Institute of Biotechnology, University of Helsinki, Helsinki, Finland. 3. Department of Neurology, Helsinki University Hospital and Department of Clinical Neurosciences (Neurology), University of Helsinki, Helsinki, Finland. 4. Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 5. German Center for Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany. 6. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. 7. Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany. 8. Geriatric Center at the University Hospital Tübingen, Tübingen, Germany.
Abstract
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. ANN NEUROL 2020;88:320-331.
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. ANN NEUROL 2020;88:320-331.
Authors: Daniela Berg; Per Borghammer; Seyed-Mohammad Fereshtehnejad; Sebastian Heinzel; Jacob Horsager; Eva Schaeffer; Ronald B Postuma Journal: Nat Rev Neurol Date: 2021-04-20 Impact factor: 42.937
Authors: Peipei Li; Bryan A Killinger; Elizabeth Ensink; Ian Beddows; Ali Yilmaz; Noah Lubben; Jared Lamp; Meghan Schilthuis; Irving E Vega; Randy Woltjer; J Andrew Pospisilik; Patrik Brundin; Lena Brundin; Stewart F Graham; Viviane Labrie Journal: Metabolites Date: 2021-01-04