Abstract / Summary
Parkinson’s disease (PD) is increasingly recognized as a heterogeneous neurodegenerative disorder with multiple clinical and pathological trajectories. In a subset of patients, α-synuclein pathology may begin in the gut and subsequently spread to the brain, a pathway most relevant to the proposed body-first subtype of PD. Tea catechins, particularly epigallocatechin-3-gallate (EGCG), can influence α-synuclein aggregation, oxidative stress, inflammatory signaling, and gut microbial ecology. Because their systemic bioavailability is limited, substantial amounts reach the intestine and undergo microbiota-dependent biotransformation. This review examines whether parent catechins and their microbial metabolites could modify intestinal processes relevant to α-synuclein misfolding and seeding. Evidence indicates that catechins are converted into phenyl-γ-valerolactones and lower-molecular-weight phenolic metabolites, while microbial amyloids such as curli can promote α-synuclein aggregation in experimental models. EGCG can also remodel α-synuclein assemblies, and catechin exposure can alter microbial and inflammatory phenotypes. However, direct evidence that catechin-derived microbial metabolites inhibit curli–α-synuclein cross-seeding or reduce enteric α-synuclein seeding remains limited. By distinguishing general neuroprotection from effects on aggregation, seeding, and disease modification, this review integrates current evidence and highlights the potential relevance of microbiota-dependent catechin metabolism to gut-origin α-synuclein pathology and body-first PD.