Differences in the Composition of Gut Microbiota between Patients with Parkinson’s Disease and Healthy Controls: A Cohort Study Original paper

What was studied?

This prospective cohort study investigated the differences in gut microbiota composition between patients with Parkinson’s disease (PD) treated exclusively with Levodopa and age-matched healthy controls. The researchers aimed to identify specific microbial taxa and diversity alterations in PD patients that could inform the understanding of PD pathogenesis and support the development of microbiome-based diagnostic or therapeutic strategies. Fecal samples from both groups were subjected to next-generation sequencing (NGS) targeting the 16S rRNA gene, enabling comprehensive identification and quantification of bacterial populations. The analysis included measures of alpha and beta diversity, taxonomic profiling at multiple levels, and statistical assessment of microbial abundance differences, with an emphasis on identifying PD-specific microbiome signatures.

Who was studied?

The study enrolled 27 hospitalized Polish patients with well-controlled idiopathic Parkinson’s disease, all receiving Levodopa monotherapy, from a single academic hospital between July 2019 and July 2020. Patients underwent extensive clinical characterization, including cognitive and functional assessments (MoCA, MMSE, H&Y, MDS-UPDRS III), and exclusion criteria eliminated individuals with other neurologic, autoimmune, inflammatory, psychiatric, or gastrointestinal diseases, recent antibiotic/probiotic use, or major gastrointestinal surgery. The control group comprised 44 age-matched healthy individuals without histories of neurological, immunological, or gastrointestinal disorders. Both groups were comparable in sex, ethnicity, and lifestyle factors, minimizing confounding variables related to demographic and clinical backgrounds.

Most important findings

The most striking findings were significant differences in both the diversity and structure of gut microbiota between PD patients and healthy controls. PD patients exhibited higher alpha and beta diversity, indicating increased richness and heterogeneity of gut bacterial communities. Taxonomic profiling revealed a greater relative abundance of the phylum Bacteroidetes (27% vs. 20%) and a lower abundance of Firmicutes (59% vs. 69%) in PD patients compared to controls. Actinobacteria remained similar (8%) in both groups. At the class level, PD patients had increased Corynebacteria (Actinobacteria) and Deltaproteobacteria (Proteobacteria).

LEfSe analysis identified several genera and species enriched in PD patients: Butyricimonas, Robinsoniella, and Flavonifractor at the genus level, and Akkermansia muciniphila, Eubacterium biforme, and Parabacteroides merdae at the species level. These taxa have been implicated in mucin degradation, gut barrier disruption, and pro-inflammatory processes. Conversely, healthy controls had higher levels of well-known butyrate-producing genera such as Faecalibacterium, Ruminococcus, and Blautia, which are associated with anti-inflammatory effects and gut health. The observed shifts suggest that PD is associated with an enrichment of mucin-degrading and potentially pro-inflammatory bacteria, alongside a depletion of beneficial butyrogenic taxa. Notably, the presence of Akkermansia muciniphila, a key mucin-degrader, was highlighted as a potential contributor to increased gut permeability and systemic inflammation in PD.

Key implications

This study reinforces the concept that Parkinson’s disease is associated with a distinct gut microbiome signature, characterized by increased microbial diversity and compositional shifts favoring mucin-degrading and pro-inflammatory taxa. The enrichment of Akkermansia muciniphila and the depletion of butyrate-producing genera such as Faecalibacterium and Blautia may contribute to gut barrier dysfunction, low-grade inflammation, and possibly the progression or symptomatology of PD. These findings lay the groundwork for the development of a microbiome signatures database for PD and highlight potential microbial biomarkers for diagnosis, risk stratification, or therapeutic intervention. Clinically, this knowledge supports the exploration of microbiome-targeted therapies—such as probiotics, prebiotics, or dietary interventions—to restore gut microbial balance and mitigate PD-related non-motor and possibly motor symptoms. Further large-scale, multicenter studies are needed to validate these microbial signatures, clarify causality, and inform personalized microbiome-modulating approaches in PD management.

Citation

Zapala B, Stefura T, Wójcik-Pędziwiatr M, Kabut R, Bałajewicz-Nowak M, Milewicz T, Dudek A, Stój A, Rudzińska-Bar M. Differences in the Composition of Gut Microbiota between Patients with Parkinson’s Disease and Healthy Controls: A Cohort Study. J Clin Med. 2021;10(23):5698. doi:10.3390/jcm10235698