Cross-Sectional Study on the Gut Microbiome of Parkinson’s Disease Patients in Central China Original paper

What was studied?

This study investigated gut microbiome alterations in Parkinson’s disease (PD) patients in central China using high-resolution shotgun metagenomic sequencing. The research aimed to identify taxonomic and functional differences in the gut microbiome between PD patients and healthy controls, specifically the patients’ spouses, to minimize confounding by diet or lifestyle. The focus keyphrase “gut microbiome in Parkinson’s disease” is central to this investigation, as the researchers sought to elucidate disease-specific microbial signatures, metabolic pathways, and associations with clinical parameters such as disease duration and severity. The study further explored the potential of microbiome-derived biomarkers for PD diagnosis and examined microbial gene functions relevant to disease mechanisms, including those affecting short-chain fatty acid (SCFA) metabolism and immune modulation.

Who was studied?

The study enrolled 39 individuals diagnosed with PD and their 39 healthy spouses as matched controls. All subjects were recruited from the Neurology Department of Xiangyang No. 1 People’s Hospital, central China. The use of spouse pairs aimed to control for shared environmental and dietary factors, thereby isolating the influence of PD on the gut microbiome. Participants were carefully screened: PD diagnosis followed Movement Disorder Society criteria, and exclusion criteria included recent antibiotic/probiotic use, serious gastrointestinal disease, severe mental disorder, and coagulopathies. The PD cohort had a mean age of approximately 64 years, with varying disease durations and severities. Clinical data collected included Hoehn and Yahr (H&Y) stage and Unified Parkinson’s Disease Rating Scale (UPDRS-III) scores.

Most important findings

The study revealed significant alterations in the gut microbiome of PD patients compared to controls at multiple taxonomic levels. Notably, diversity indices (Shannon and Chao1) were higher in the PD group, suggesting overgrowth of pathogenic taxa rather than a healthy microbiome. At the phylum level, Actinobacteria and Synergistetes were significantly increased in PD. At lower taxonomic levels, enrichment was observed for Bilophila wadsworthia—a novel finding for PD—along with Desulfovibrio, Scardovia, and Alistipes, while Bacteroides was enriched in controls. The family Bifidobacteriaceae was also elevated in PD. Phage abundance was higher in PD, though plasmid abundance did not differ, indicating potential shifts in mobile genetic elements.

A random forest classifier using the top 20 discriminatory genera achieved an area under the receiver operating characteristic curve (AUC) of 0.803, demonstrating the diagnostic potential of microbiome signatures for PD. Importantly, Klebsiella and Parasutterella abundances were positively correlated with disease duration and severity, whereas hydrogen-generating Prevotella was negatively correlated with disease severity, implying a protective role.

Functional gene analyses showed that branched-chain amino acid (BCAA) transport system proteins were significantly increased, while carbohydrate-active enzyme family GH43 was decreased in PD. Pathway analysis indicated altered SCFA precursor metabolism, with the acetyl-CoA fermentation to butanoate II pathway enriched in PD, suggesting changes in neuroactive metabolite production. Thirteen metabolic pathways, including amino acid biosynthesis and energy metabolism, differed significantly between groups.

Key implications

This study provides robust evidence that the gut microbiome in Parkinson’s disease harbors distinct taxonomic and functional signatures, with potential applications for non-invasive biomarker development and personalized interventions. The enrichment of Bilophila wadsworthia in PD patients implicates new pro-inflammatory and barrier-disrupting pathways, while the reduction in hydrogen-generating Prevotella aligns with hypotheses about impaired neuroprotection and gut-brain axis dysfunction in PD. Functional alterations in BCAA transport and SCFA metabolism further highlight possible mechanistic links between gut dysbiosis and PD pathophysiology, including neuroinflammation and metabolic derangements. These findings reinforce the concept of a proinflammatory dysbiotic state in PD and suggest that targeted modulation of the gut microbiome could become a therapeutic avenue. The use of shotgun metagenomics enabled higher taxonomic and functional resolution than previous 16S rRNA studies, setting a new standard for microbiome research in neurodegenerative diseases.

Citation

Mao L, Zhang Y, Tian J, Sang M, Zhang G, Zhou Y, Wang P. Cross-Sectional Study on the Gut Microbiome of Parkinson’s Disease Patients in Central China. Front Microbiol. 2021;12:728479. doi:10.3389/fmicb.2021.728479