Plasma branched-chain and aromatic amino acids correlate with the gut microbiota and severity of Parkinson's disease.

Disturbances of circulating amino acids have been demonstrated in patients with Parkinson's disease (PD). However, there have been no consistent results for branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), and related factors have not been explored. We aimed to explore plasma BCAA and AAA profiles in PD patients, and identify their correlations with clinical characteristics and the gut microbiota. Plasma BCAA (leucine, isoleucine, and valine) and AAA (tyrosine and phenylalanine) levels were measured in 106 PD patients and 114 controls. Fecal samples were collected from PD patients for microbiota sequencing and functional analysis. We found that plasma BCAAs and tyrosine were decreased in PD patients. BCAAs and AAAs were correlated with clinical characteristics and microbial taxa, and, in particular, they were negatively correlated with the Hoehn and Yahr stage. Compared with early PD patients, BCAA and AAA levels were even lower, and microbial composition was altered in advanced PD patients. Predictive functional analysis indicated that predicted genes numbers involved in BCAA biosynthesis were lower in advanced PD patients. What's more, the fecal abundances of critical genes (ilvB, ilvC, ilvD, and ilvN) involved in BCAA biosynthesis were reduced and fecal BCAA concentrations were lower in advanced PD patients. In conclusion, the disturbances of plasma BCAAs and AAAs in PD patients may be related to the gut microbiota and exacerbated with PD severity. The microbial amino acid metabolism may serve as a potential mechanistic link.