The Associations Among Gut Microbiota, Branched Chain Amino Acids, and Parkinson's Disease: Mendelian Randomization Study.

BACKGROUND

In experimental and observational studies, the characteristics of gut microbiota have been associated with Parkinson's disease (PD), among which metabolic pathways played an important role. However, the causality remained unclear.

OBJECTIVE

Herein, we aimed to determine the potential impact of gut microbiota and gut microbiota-derived metabolites on PD risk using a Mendelian randomization (MR) approach.

METHODS

We included as exposures gut microbial taxa abundance and gut-derived metabolites (branched chain amino acids [BCAAs]), with PD as the outcome. In addition, we explored whether BCAAs act as a mediating factor in the pathway from gut microbiota to PD.

RESULTS

We found evidence of a causality of 15 microbial taxa and PD before and after sensitivity analyses, but not after multiple testing correction. There was significant association between BCAAs levels and the risk of PD, especially isoleucine (OR = 0.995, 95% CI 0.992-0.999, p = 0.004, pFDR = 0.012). In addition, the causality of gut microbiota and BCAAs was also explored that the increased g_Coprococcus abundance can result in the decrease in isoleucine level (OR = 1.046; 95% CI, 1.009-1.085; p = 0.016).

CONCLUSIONS

Our findings indicated suggestive association between gut microbiota and its metabolites and PD. Furthermore, higher BCAAs levels were associated with the decreased PD risk. This study may provide new targets for PD treatment, such as dietary BCAAs supplementation.