Gut microbiota across early stages of alpha-synucleinopathy

It has been an ongoing debate about the causal relationship between gut dysbiosis and Parkinson's disease (PD), partially due to the high variability of gut microbiota (sensitive to host lifestyle and physiological characteristics) and the difficulties in identifying subjects with prodromal syndrome of PD. Here, we investigated gut microbiota across early PD, REM sleep behavior disorder (RBD, pre-PD), high-risk first-degree relatives of RBD (pre-RBD), and controls, which simulated the gut-brain staging model of PD. We find that the depletion of short-chain fatty acids-producing bacteria and overabundance of bacteria inducing gut barrier disruptions, have already emerged in RBD subjects and their relatives. These results remained robust even after stratifying potential confounders, such as obesity and constipation symptoms. Overall, this finding suggests that PD-like gut dysbiosis occurs before the onset of RBD and PD. Interventions targeting at specific microbes will be critical for early prevention and disease-modifying therapies of PD.