# Alterations of fecal microbiota and plasma metabolome in patients with Parkinson’s disease with rapid eye movement sleep disorder

## TL;DR

This study explores gut microbiota and blood metabolites in Parkinson’s disease patients with and without sleep disorders, revealing potential biomarkers and metabolic pathways linked to disease progression.

## Contribution

The study identifies specific gut bacteria and metabolites associated with Parkinson’s disease with rapid eye movement sleep behavior disorder (PD-RBD), offering new insights into its pathogenesis.

## Key findings

- Lactobacillaceae, Christensenellaceae, and Fusobacteriaceae were significantly different in PD-RBD, PD-nRBD, and healthy controls.
- 3-methoxy-4-hydroxyphenylglycol sulfate positively correlated with Lactobacillus in PD-RBD patients.
- Distinct microbiota and metabolites were linked to phenylalanine and vitamin B6 metabolism.

## Abstract

Patients with Parkinson’s disease (PD) with probable rapid eye movement sleep behavior disorder (RBD) (PD-RBD), a specific subtype of PD, are characterized by the presence of more severe motor and non-motor symptoms. This study aimed to elucidate the characteristics and interactions of gut microbiota and plasma metabolic characteristics of PD-RBD, thus screening for the disease mechanisms. A total of 100 PD patients, 50 healthy controls (HCs) and 16 probable idiopathic RBD (iRBD) patients were collected. There were 33 PD-RBD and 67 patients without probable RBD (PD-nRBD) in PD patients. DNA extraction, PCR amplification, and high-throughput sequencing were used for intestinal microbiota analysis, and ultra-high liquid chromatography tandem mass spectrometry was used for metabolome analysis. Spearman analysis was applied to investigate the correlation of fecal microbiota and plasma metabolome. Our findings revealed Lactobacillaceae (P = 0.017), Christensenellaceae (P = 0.017), Fusobacteriaceae (P = 0.018), Lactobacillus (P = 0.035), Christensenellaceae R-7 group (P = 0.035), and Fusobacterium (P = 0.035) were significantly different in PD-RBD, PD-nRBD, and HC. Moreover, the differential metabolites identified in both PD-nRBD and PD-RBD were 3-hydroxy-2-methylpyridine-4,5-dicarboxylate (VIP = 5.802) and 3-methoxy-4-hydroxyphenylglycol sulfate (VIP = 5.732). Furthermore, our analysis revealed that 3-methoxy-4-hydroxyphenylglycol sulfate showed a positive correlation with Lactobacillus (r = 0.197, P = 0.049). Finally, functional analysis indicated that these distinctive microbiota and metabolites were primarily associated with phenylalanine metabolism and vitamin B6 metabolism. We managed to show that the differential microbiota, differential metabolites, and their interactions in PD-RBD compared to PD-nRBD and HC. This furthers our understanding of disease pathogenesis, and offers fresh perspectives on its detection and treatment.

There are currently fewer investigations on the intestinal microbiota and metabolites of probable rapid eye movement sleep behavior disorder (PD-RBD) and idiopathic RBD (iRBD). Our findings indicate that PD-RBD exhibits an increase in Christensenellaceae and 3-methoxy-4-hydroxyphenethyleneglycol sulfate, and that iRBD exhibits a similar trend. This suggests that the PD prodromal stage may have seen this alteration. Furthermore, functional analysis indicated that these distinctive microbiota and metabolites were primarily associated with phenylalanine metabolism and vitamin B6 metabolism. Basic experiments and multi-center, large-cohort clinical researches are worth conducting to confirm this, since they may offer insights for treating individuals with PD-RBD.