Idiopathic Rapid Eye Movement Sleep Behavior Disorder (iRBD) Shares Similar Fecal Short‐Chain Fatty Acid Alterations with Multiple System Atrophy (MSA) and Parkinson's Disease (PD)

Abstract Background Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered as a prodromal stage of synucleinopathies. Fecal short‐chain fatty acid (SCFA) changes in iRBD and the relationships with synucleinopathies have never been investigated. Objectives To investigate fecal SCFA changes among iRBD, multiple system atrophy (MSA), and Parkinson's disease (PD), and evaluate their relationships. Methods Fecal SCFAs and gut microbiota were measured in 29 iRBD, 42 MSA, 40 PD, and 35 normal controls (NC) using gas chromatography–mass spectrometry and 16S rRNA gene sequencing. Results Compared with NC, fecal SCFA levels (propionic, acetic, and butyric acid) were lower in iRBD, MSA, and PD. Combinations of these SCFAs could differentiate NC from iRBD (AUC 0.809), MSA (AUC 0.794), and PD (AUC 0.701). Decreased fecal SCFAs were associated with the common reducing SCFA‐producing gut microbiota in iRBD, MSA, and PD. Conclusions iRBD shares similar fecal SCFA alterations with MSA and PD, and the combination of these SCFAs might be a potential synucleinopathies‐related biomarker. © 2024 International Parkinson and Movement Disorder Society.