Machine learning-based meta-analysis reveals gut microbiome alterations associated with Parkinson’s disease

Abstract There is strong interest in exploring the potential of the gut microbiome for Parkinson’s disease (PD) diagnosis and treatment. However, a consensus on the microbiome features associated with PD and a multi-study assessment of their diagnostic value is lacking. Here, we present a machine learning meta-analysis of PD microbiome studies of unprecedented scale (including 4,490 samples). Within most studies, microbiome-based machine learning models could accurately classify PD patients. However, models were study-specific and did not generalise well across other studies. By training models on multiple datasets, we could improve their general applicability and disease specificity as assessed against microbiomes from other neurodegenerative diseases. Meta-analysis of shotgun metagenomes moreover delineated PD-associated microbial pathways potentially contributing to the deterioration of gut health and favouring the translocation of pathogenic molecules along the gut-brain axis. Strikingly, diverse microbial pathways for the biotransformation of solvents and pesticides were enriched in PD. These results align with the epidemiological evidence that exposure to these molecules increases PD risk and raise the question of whether gut microbial metabolism modulates their toxicity. Taken together, we offer the most comprehensive overview to date about the PD gut microbiome and provide future reference for its diagnostic and functional potential.