From dysbiosis to dysfunction: specific gut microbes and metabolites in the pathogenesis of Parkinson's disease.

Abstract

Parkinson's disease (PD) involves a complex interplay between the gut microbiota, their metabolites, and host neurophysiology. Studies across independent cohorts have begun to reveal reproducible microbial signatures, with taxa such as Desulfovibrio spp., Akkermansia, and Bifidobacterium repeatedly enriched, whereas Prevotellaceae and Faecalibacterium are consistently reduced. Beyond these broad compositional patterns, several species and strains-including Helicobacter pylori, curli-producing Escherichia coli, and Desulfovibrio spp.-have been linked to processes such as α-synuclein aggregation, immune activation, and dopaminergic vulnerability. Microbial metabolites including short-chain fatty acids, hydrogen sulfide, lipopolysaccharides, bile acids, and iron-related compounds provide additional mechanistic connections, influencing gut barrier function, inflammatory responses, and neuronal homeostasis. In this review, we bring together findings from taxonomic, metabolic, and mechanistic studies, evaluate the therapeutic potential of microbiota-targeted interventions. Future research should pivot from descriptive microbiome profiling toward mechanistic studies that delineate causal relationships between defined microbes, their metabolites, and PD pathology. Such efforts are essential for identifying early diagnostic biomarkers and developing targeted microbiota-based therapies that could alter the clinical course of PD.