Reduction of Short-Chain Fatty Acid-Producing Gut Microbiota Leads to Transition from Rapid-Eye-Movement Sleep Behavior Disorder to Parkinson's Disease

Gut dysbiosis has been reported repeatedly in Parkinson9s disease (PD), but once in rapid-eye-movement sleep behavior disorder (RBD) from Germany. Abnormal aggregation of α-synuclein fibrils causing PD possibly starts from the intestine. RBD patients frequently develop PD. Early-stage gut dysbiosis that is causally associated with PD is thus expected to be observed in RBD. We analyzed gut microbiota in 26 RBD patients and 137 controls by 16S rRNA-seq. Our RBD dataset was meta-analyzed with the German RBD dataset, and was compared with gut microbiota in 223 PD patients. Unsupervised clustering of gut microbiota by LIGER, a topic model-based tool for single-cell RNA-seq analysis, revealed four enterotypes in controls, RBD, and PD. Short-chain fatty acid (SCFA)-producing bacteria were conserved in an enterotype observed in controls and RBD, whereas they were less in enterotypes observed in PD. Genus Akkermansia and family Akkermansiaceae were consistently increased in both RBD in two countries and PD in five countries. No short-chain fatty acid (SCFA)-producing bacteria were significantly changed in RBD in two counties. In contrast, we previously reported that recognized and putative SCFA-producing genera Faecalibacterium, Roseburia, and Lachnospiraceae ND3007 group were consistently decreased in PD in five countries. Increased mucin-layer-degrading genus Akkermansia possibly accounts for the development of RBD, and an additional decrease of SCFA-producing genera is likely to be associated with the transition from RBD to PD.