Distinct Changes in the Gut Microbiome of Parkinson's Patients
A number of neurodegenerative conditions have been linked to alterations in the gut microbiome, distinct from those already taking place with age. The balance of microbial populations making up the gut microbiome shifts with age to favor inflammation over production of beneficial metabolites. Researchers here make an effort to characterize gut microbiome changes associated specifically with Parkinson's disease; whether these are indicative of greater inflammation or they touch on other mechanisms that can drive neurodegeneration remains to be determined. In the context of Parkinson's, it is worth noting that evidence suggests that the misfolded α-synuclein that spreads throughout the central nervous system to drive disease progression initially appears in the intestines rather than the brain in a sizeable number of cases.
Parkinson's disease (PD) has been consistently linked to alterations within the gut microbiome. Metagenomic sequencing was used to characterize taxonomic and functional changes to the PD microbiome and to explore their relation to bacterial metabolites and disease progression. Motor and non-motor symptoms were tracked using Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and levodopa equivalent dose across ≤5 yearly study visits.
PD-derived stool samples had reduced intermicrobial connectivity and seven differentially abundant species compared to controls. A suite of bacterial functions differed between PD and controls, including depletion of carbohydrate degradation pathways and enrichment of ribosomal genes. Faecalibacterium prausnitzii-specific reads contributed significantly to more than half of all differentially abundant functional terms. A subset of disease-associated functional terms correlated with faster progression of MDS-UPDRS part IV and separated those with slow and fast progression with moderate accuracy. Most PD-associated microbial trends were stronger in those with symmetric motor symptoms.
In conclusion, we provide further evidence that the PD microbiome is characterized by reduced intermicrobial communication and a shift to proteolytic metabolism in lieu of short-chain fatty acid production, and suggest that these microbial alterations may be relevant to disease progression.