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

Abstract

Gut dysbiosis has been reported repeatedly in Parkinson's 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. Initial gut dysbiosis causally associated with PD is thus expected to be observed in RBD. We here analyzed gut microbiota in 26 RBD patients and 137 controls by 16S rRNA-seq, and meta-analyzed our dataset with the German dataset. Unsupervised clustering of gut microbiota by LIGER, a topic model-based tool for single-cell RNA-seq analysis, revealed enterotypes A-D. Enterotypes were shifted from A-to-D with transition from controls, RBD, to the disease progression of PD. Seven taxa were increased in RBD in Japan, and six of them were also increased in RBD in Japan and Germany. Among the six taxa, genus Akkermansia and family Akkermansiaceae were consistently increased in PD in five countries, and the other four taxa were also variably changed in PD. No short-chain fatty acid (SCFA)-producing bacteria were significantly changed in RBD in the meta-analysis. 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 may be associated with the transition from RBD to PD.

Assessing the Effect of Interaction Between C-Reactive Protein and Gut Microbiome on the Risks of Anxiety and Depression

“…Akkermansia muciniphila (Akk bacteria) can also degrade mucin, which is negatively related to in ammation and metabolic disorders (39,40). It is demonstrated that genus Akkermansia and family Akkermansiaceae were consistently changed in both idiopathic rapid-eyemovement sleep behavior disorder and Parkinson's disease (41). In addition, microbial community pro ling revealed reduction (e.g.…”