Oral and gut dysbiosis leads to functional alterations in Parkinson’s disease Original paper

What was studied?

This study investigated the relationship between oral and gut microbiome dysbiosis and functional alterations in individuals with Parkinson’s disease (PD), leveraging both 16S rRNA gene and whole-genome shotgun metagenomic sequencing. The primary aim was to clarify the taxonomic and functional changes in the oral and gut microbiota of PD patients compared to healthy controls, and to determine whether an oral-gut microbiome connection exists in PD. The researchers sought to identify specific microbial taxa and functional gene markers that could serve as PD-associated microbial signatures, with particular attention to glutamate and arginine metabolism, as well as antimicrobial resistance. Notably, the study compared the discriminatory power of functional and taxonomic markers for distinguishing PD from healthy states and explored the association between oral and gut microbial alterations and clinical features of PD.

Who was studied?

The research included 91 PD patients and 85 healthy controls, recruited at Asan Medical Center, South Korea, between 2019 and 2020. The healthy controls were primarily the spouses of PD patients to control for shared environmental exposures. Exclusion criteria encompassed inflammatory bowel disease, recent infection, recent antibiotic or immunosuppressant use, prior gastrointestinal or oral surgery, use of artificial nutrition, deep brain stimulation, or PD dementia. Clinical data collected included age, sex, BMI, disease duration, medication use, dietary intake, and validated assessments for constipation, dysphagia, olfactory dysfunction, and PD severity (Hoehn and Yahr stage, Unified Parkinson’s Disease Rating Scale). After quality control, 88 PD and 84 HC stool samples, and 74 PD and 69 HC oral samples were included in the microbiome analyses.

Most important findings

The study demonstrated significant differences in both oral and gut microbiota composition between PD patients and healthy controls, with high-resolution insights provided by shotgun metagenomics. In the gut, PD patients exhibited reduced abundance of beneficial short-chain fatty acid producers (e.g., Prevotella copri, Faecalibacterium spp.) and increased levels of proinflammatory or pathogenic species (e.g., Alistipes onderdonkii, Bacteroides dorei, Parabacteroides merdae, Butyrivibrio crossotus). Notably, oral Lactobacillus was consistently more abundant in PD patients, and its oral abundance correlated with higher levels of opportunistic pathogens (Citrobacter, Klebsiella, Enterobacter) and lower Faecalibacterium in the gut, but only in PD—not in controls. This supports a PD-specific oral-gut microbial axis.

Functionally, PD patients’ gut microbiota displayed marked downregulation of microbial genes involved in glutamate and arginine biosynthesis (essential for gut and brain health), while genes linked to antimicrobial and cationic antimicrobial peptide resistance were upregulated. These functional shifts were strongly correlated with specific bacterial taxa, notably the reduced Prevotella copri and Faecalibacterium species. Importantly, machine learning classifiers using functional gene markers from shotgun metagenomics (particularly genes for glutamate/arginine metabolism) outperformed taxonomic classifiers (AUC 0.88 vs. 0.74) for PD discrimination.

Microbiome alterations were also associated with clinical features: increased stool Lactobacillus and Bifidobacterium correlated with greater PD severity, and lower Prevotella with firmer stool. Medication use (amantadine) influenced gut microbial composition, and oral microbiome taxa did not directly associate with clinical symptoms.

Key implications

This study provides compelling evidence for a functional oral-gut microbiome axis in Parkinson’s disease, characterized by distinct taxonomic and metabolic shifts not seen in healthy controls. The enrichment of oral Lactobacillus and its association with gut dysbiosis in PD highlights a potentially modifiable microbial signature with diagnostic and therapeutic relevance. The pronounced reduction in microbial genes for glutamate and arginine biosynthesis suggests that PD-associated microbiota may contribute to both gut inflammation and neurodegeneration, possibly via altered amino acid metabolism and increased antimicrobial resistance. These findings underscore the superiority of shotgun metagenomics and functional profiling for identifying clinically meaningful microbiome signatures in PD. Future research should explore causality, the potential of oral microbiota as a non-invasive biomarker, and therapeutic modulation of these microbial pathways to impact PD progression.

Citation

Jo S, Kang W, Hwang YS, Lee SH, Park KW, Kim MS, Lee H, Yoon HJ, Park YK, Chalita M, Lee JH, Sung H, Lee JY, Bae JW, Chung SJ. Oral and gut dysbiosis leads to functional alterations in Parkinson’s disease. npj Parkinson’s Disease. 2022;8:87. doi:10.1038/s41531-022-00351-6