Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions Original paper
Researched by:
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Dr. Umar
ID
Dr. Umar
Read MoreClinical Pharmacist and Clinical Pharmacy Master’s candidate focused on antibiotic stewardship, AI-driven pharmacy practice, and research that strengthens safe and effective medication use. Experience spans digital health research with Bloomsbury Health (London), pharmacovigilance in patient support programs, and behavioral approaches to mental health care. Published work includes studies on antibiotic use and awareness, AI applications in medicine, postpartum depression management, and patient safety reporting. Developer of an AI-based clinical decision support system designed to enhance antimicrobial stewardship and optimize therapeutic outcomes.
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Dr. Umar
Read More
Researched by:
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Dr. Umar
ID
Dr. Umar
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
Location
Luxembourg
Sample Site
Feces
Species
Homo sapiens
What was studied?
This study investigates parkinsons-disease-gut-microbiome-metabolic-functions by combining 16S rRNA stool sequencing with personalised genome-scale metabolic modelling in people with Parkinson’s disease (PD) and matched controls. The authors analysed gut microbial composition (genus and species levels) and then used the AGORA/COBRA modelling framework to predict community-wide secretion potentials for 129 microbial metabolites under a standard European diet. Their goal was to link taxonomic shifts to functional metabolic outputs, particularly pathways relevant to sulfur metabolism, γ-aminobutyric acid (GABA), and vitamins such as pantothenic acid.
Who was studied?
Participants were drawn from the Luxembourg Parkinson’s Study, a monocentric national cohort. The analysis focused on 147 individuals with clinically typical PD and 162 healthy controls, all older than 50 years. PD diagnosis followed UK Brain Bank criteria, while controls were largely spouses or volunteers rigorously screened to exclude Parkinsonism, major neurological disease, and confounders such as recent antibiotic use or dopaminergic medication. After excluding those with missing body mass index (BMI) data, 308 subjects were included in microbiome and covariate-adjusted analyses. PD participants spanned Hoehn and Yahr stages with substantial variation in disease duration (mean ~6 years), motor disability, and non-motor symptom burden. Constipation affected roughly 37% of PD patients but only 6% of controls, offering a clinically relevant axis to examine microbiome–symptom relationships.
Most important findings
| Topic | Details |
|---|---|
| Community composition | Beta diversity (Bray–Curtis) differed modestly but significantly between PD and controls; alpha diversity showed only slight richness increase in PD. Eight genera and seven species were significantly altered after adjustment for age, sex, BMI, batch, and read depth. PD was enriched in Akkermansia, Christensenellaceae-related genera, Lactobacillus, Bilophila, Streptococcus, Acidaminococcus, and specific Ruminococcus and Roseburia species, with Turicibacter and Paraprevotella reduced. Akkermansia muciniphila showed the strongest enrichment (~80% higher odds of reads in PD), consistent with earlier PD cohorts. |
| Disease–covariate interactions | Disease–covariate effects were marked. Paraprevotella reduction was largely confined to women with PD, indicating sex-specific signatures. In PD, constipation associated with increased Bifidobacterium, contrasting with some non-PD constipation cohorts. Bilophila and Paraprevotella abundances tracked Hoehn and Yahr stage: Bilophila rose and Paraprevotella fell with greater motor disability. Higher UPDRS III scores were linked to increased Flavonifractor and Peptococcus and decreased Paraprevotella, implying several taxa reflect clinical severity beyond simple PD vs control status. |
| Metabolites and constipation | Metabolic modelling showed PD microbiomes had distinct net maximal production capacities (NMPCs) for nine metabolites. PD samples had higher predicted production of sulfur-related metabolites (methionine, cysteinylglycine), plus D-alanine, D-ribose, mannitol, L-lactate, xanthine, 4-hydroxybenzoate, and uracil. NMPCs for xanthine, D-alanine, L-lactate, pantothenic acid, and D-ribose were elevated in constipated individuals. Pantothenic acid NMPC positively correlated with non-motor symptom scores in both PD and controls, linking microbial metabolism to broader symptom burden. |
| Akkermansia as metabolic hub | Akkermansia acted as a metabolic hub: its abundance explained substantial variance in predicted secretion of multiple metabolites, including GABA, hydrogen sulfide, and methionine. GABA secretion potential was nominally higher in PD and showed a strong, nonlinear relationship with Akkermansia abundance, suggesting complex, non-proportional scaling of microbiome-derived neurotransmitter-related functions in Parkinson’s disease. |
Key implications
Clinically, this work reinforces PD as a gut–brain–metabolism disorder rather than a purely central dopaminergic disease. The specific microbial signatures—enrichment of Akkermansia, Lactobacillus, Bilophila, Christensenella and depletion of Turicibacter and Paraprevotella, with sex- and constipation-dependent modulation—provide candidates for microbiome signature databases focused on PD. Functionally, the predicted upregulation of sulfur pathways (methionine, cysteinylglycine, hydrogen sulfide) and GABA, and the link between pantothenic acid production and non-motor burden, align with independent metabolomics work and point to microbially driven perturbations in bile acid, taurine, and neurotransmitter biochemistry. For clinicians, these findings support viewing gut microbial patterns as correlates—and potentially contributors—to motor severity and non-motor symptoms, opening avenues for stratification, targeted probiotic/prebiotic interventions, and integration of gut-derived metabolic readouts into PD management once causality and therapeutic modifiability are clarified.
Citation
Baldini F, Hertel J, Sandt E, et al; NCER-PD Consortium. Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions. BMC Biology. 2020;18(1):62. doi:10.1186/s12915-020-00775-7