Integrated Microbiome and Host Transcriptome Profiles Link Parkinson’s Disease to Blautia Genus: Evidence From Feces, Blood, and Brain Original paper

What was studied?

This original research article investigated the relationship between the microbiome and Parkinson’s disease (PD) by integrating microbiota and host transcriptome profiles across three body compartments: feces, blood, and brain. The primary aim was to identify key microbial genera consistently associated with PD and to explore their potential mechanistic links to disease pathogenesis. Leveraging publicly available sequencing datasets, the authors conducted a thorough meta-analysis of 16S rRNA and RNA-Seq data, filtered for contaminants, to characterize microbiota composition and host gene expression. Functional prediction analyses and machine learning models (random forest classifiers) were used to identify and validate microbial signatures discriminative of PD, with a particular focus on the genus Blautia and its association with neurodegenerative and metabolic pathways.

Who was studied?

The study synthesized data from a large cohort, encompassing 2,883 participants pooled from 16 independent projects. These included ten fecal microbiome studies (1,914 samples after deduplication and cleaning), one blood microbiome study (86 samples), and five brain studies utilizing RNA-Seq for both microbiome and transcriptome profiling (376 samples). The participants were all human subjects, including both PD patients and healthy controls. The studies spanned diverse geographic locations, including the United States, Japan, Germany, Denmark, Finland, China, Israel, Italy, and the Netherlands. Metadata such as age, sex, and body mass index (BMI) were included where available, but not uniformly across all datasets. The integration of multiple sample types and platforms allowed for a comprehensive cross-tissue meta-analysis, with efforts made to control for batch effects and contaminant taxa.

Most important findings

A central discovery of this study was that the genus Blautia, belonging to the Firmicutes phylum, was uniquely and significantly depleted in PD patients across all three sampled compartments: feces, blood, and brain. This finding held true after rigorous removal of potential contaminants and was validated using multiple reference databases and analytical approaches, including both 16S rRNA and shotgun metagenomics data. At the species level, several Blautia species (B. argi, B. coccoides, B. sp. SC05B48, B. hansenii) were found to be reduced in the feces of PD patients.

In the fecal microbiome, PD was associated with a higher Firmicutes/Bacteroidetes ratio, increased alpha diversity, and distinct beta diversity compared to controls. However, such differences were not observed in blood or brain samples, suggesting a unique gut microbial signature in PD. Functional prediction of the altered microbiome indicated enrichment in pathways related to neurodegenerative diseases, inflammation, and energy metabolism.

Integration of microbiome and host transcriptome data from brain samples revealed that genes correlated with Blautia abundance were predominantly involved in mitochondrial function, energy metabolism, immune response, and protein degradation. KEGG and GO enrichment analyses linked these genes to key neurodegenerative pathways (including PD, Alzheimer’s, Huntington’s, and ALS) and metabolic diseases (such as diabetic cardiomyopathy and NAFLD). Notably, several differentially expressed genes (DEGs) associated with Blautia were previously implicated in PD pathogenesis.

Machine learning models further supported the discriminative value of Blautia depletion: a random forest classifier using fecal microbiota data achieved an ROC-AUC of 0.704 and a PRC-AUC of 0.787 in distinguishing PD patients from controls, with Blautia ranking among the top discriminatory features.

Key implications

This study provides robust evidence that depletion of the genus Blautia is a reproducible and cross-compartmental microbiome signature of Parkinson’s disease. The consistent reduction of Blautia in feces, blood, and brain highlights its potential as a non-invasive biomarker for PD diagnosis and progression monitoring. The strong association between Blautia abundance and host gene expression in pathways central to neurodegeneration and metabolism suggests a mechanistic link, possibly involving mitochondrial dysfunction and inflammation. These findings support the hypothesis that gut microbiota alterations can have systemic and neurobiological consequences, opening avenues for therapeutic intervention targeting Blautia or its metabolic products (e.g., butyrate and acetate). The study also underscores the necessity of rigorous contaminant control and multi-omics integration in microbiome research related to neurodegenerative diseases.

Citation

Guo X, Tang P, Hou C, Chong L, Zhang X, Liu P, Chen L, Liu Y, Zhang L, Li R. Integrated Microbiome and Host Transcriptome Profiles Link Parkinson’s Disease to Blautia Genus: Evidence From Feces, Blood, and Brain. Front Microbiol. 2022;13:875101. doi:10.3389/fmicb.2022.875101