Linking diet, gut microbiota, and metabolites to Parkinson's disease risk: a shotgun metagenomic comparison of Japanese and Taiwanese cohorts.

Emerging evidence suggests that gut microbiota and its metabolites play pivotal roles in the pathogenesis of Parkinson's disease (PD). However, cross-national differences in diet and microbial composition may account for the striking variability in PD prevalence worldwide. To address this, we performed a comparative shotgun metagenomic analysis between Japanese and Taiwanese individuals, two genetically similar East Asian populations with distinct dietary habits and differing PD incidence rates. Our analysis revealed marked differences in dietary intake: Taiwanese individuals consumed higher amounts of animal fats and tropical fruits, whereas the Japanese diet was characterized by greater intake of seafood, root vegetables, and traditional fermented foods such as natto. These dietary patterns were reflected in gut microbiota profiles. Japanese individuals exhibited a higher abundance of Blautia, Faecalibacterium, and Bifidobacterium, while Taiwanese samples were enriched in Bacteroides and Alistipes. Functionally, genes involved in short-chain fatty acid (SCFA), vitamin, and polyamine biosynthesis were significantly reduced in PD patients and in the Taiwanese cohort. Metabolomic analyses corroborated these findings, showing decreased levels of SCFAs, polyamines, and key vitamins such as nicotinate and pantothenate in PD patients. Notably, Blautia abundance correlated positively with a broad range of beneficial metabolites, highlighting its potential role as a central modulator of host-microbe metabolic interactions. Our findings suggest that traditional Japanese dietary practices may shape a gut microbial environment that confers resistance to PD, underscoring the need for future interventional studies targeting diet-microbiota interactions in PD prevention and treatment.