Changes in the Gut Microbiome and Predicted Functional Metabolic Effects in an Australian Parkinson’s Disease Cohort Original paper

What was studied?

This original study investigated the gut microbiome in Australian Parkinson’s disease and how microbial alterations in people with Parkinson’s disease (PwP) may influence functional metabolic pathways relevant to neurodegeneration. Using 16S rRNA sequencing of the V3–V4 regions, the researchers compared microbial composition, alpha and beta diversity, and predicted KEGG metabolic pathways between 87 PwP and 47 healthy controls. The analysis focused on identifying bacterial signatures, especially shifts toward pro-inflammatory taxa, altered short-chain fatty acid (SCFA) producers, and functional metabolic disruptions linked to amino acid and bile acid pathways. The study uniquely addressed geographical variability by characterizing a southern hemisphere cohort, aiming to expand understanding of microbiome-based mechanisms underlying Parkinson’s disease and its gastrointestinal prodrome.

Who was studied?

The research included 87 individuals with idiopathic Parkinson’s disease from several Australian movement disorders clinics and 47 age-matched controls without neurological disease. Participants were assessed with validated GI symptom scales, Parkinson’s motor assessments, and comprehensive medication histories. Importantly, none had taken antibiotics in the prior three months, and stool samples were processed under standardized laboratory conditions. The PwP cohort showed higher constipation burden, greater GI symptom severity, and typical PD medication exposure patterns. This population enabled a detailed comparison of disease-related microbial signatures independent of major confounders such as inflammatory bowel disease or recent antimicrobial use.

Most important findings

The study revealed a distinct gut microbiome in Australian Parkinson’s disease, including reduced alpha diversity in PwP and significant phylum-to-genus-level taxonomic shifts. PwP demonstrated increases in Proteobacteria and Synergistetes—phyla associated with pro-inflammatory and pathogenic activity—alongside consistent reductions in multiple Firmicutes genera known for SCFA production (Roseburia, Agathobaculum, Kineothrix, Colidextribacter, Intestinibacter). The loss of Lachnospiraceae family members paralleled known declines in butyrate-producing taxa observed in Northern Hemisphere PD cohorts.

At the functional level, KEGG pathway predictions showed 26 pathways significantly altered. Upregulated pathways included lysine degradation, tryptophan metabolism, and branched-chain amino acid degradation, all linked to mitochondrial stress, neuroinflammation, and impaired neurotransmitter synthesis. Downregulated pathways included primary and secondary bile acid biosynthesis, suggesting impaired cholesterol metabolism, reduced microbial conversion of bile acids, and potential contributions to constipation or small intestinal bacterial overgrowth.

Key implications

Together, these findings indicate that Australian PwP exhibit a dysbiotic microbial profile marked by inflammatory taxa expansion, depletion of SCFA-producing genera, and altered metabolic functions. Decreased butyrate producers may weaken gut barrier integrity, amplify inflammation, and influence α-synuclein aggregation. Downregulated bile acid biosynthesis may worsen motility issues and contribute to microbial overgrowth. Increased tryptophan metabolism suggests heightened IDO-1 activity, potentially reducing serotonin availability in the gut and brain, with implications for mood, motility, and sleep disturbances in PD. These microbial signatures reinforce the gut–brain axis as a mechanistic contributor to Parkinson’s pathogenesis and highlight potential targets for microbiome-informed diagnostics or therapeutics.

Citation

Kenna JE, Chua EG, Bakeberg M, Tay A, McGregor S, Gorecki A, et al. Changes in the gut microbiome and predicted functional metabolic effects in an Australian Parkinson’s disease cohort.Frontiers in Neuroscience. 2021;15:756951. doi:10.3389/fnins.2021.756951