In this exploratory cross-sectional study of 21 iRBD patients and 15 healthy controls, integrated fecal metabolomics and 16S microbiome profiling identified candidate signatures of a shift toward proteolytic fermentation, reduced tryptophan-indole metabolism, bile acid depletion, and altered microbiota that discriminated iRBD from controls (84.8% cross-validated accuracy), but these findings are hypothesis-generating given the limited sample size.
Linear short-chain fatty acids were preserved in iRBD, whereas branched-chain fatty acids were selectively increased.
Volatilomic profiling showed reduced indole and increased p-cresol and 2-octanone in iRBD feces.
Untargeted LC-MS/MS of the non-volatile fraction showed attenuation of the tryptophan-indole axis, class-level bile acid depletion, and increased acylcarnitines in iRBD.
The gut microbiome of iRBD patients was depleted of Blautia and Faecalibacterium and enriched in Oscillospirales.
DIABLO multi-omics integration of metabolomic and microbial layers produced a host-microbe signature that discriminated iRBD patients from controls.
The findings are exploratory and hypothesis-generating; the value of these signatures for predicting phenoconversion remains unestablished.
Isolated REM sleep behavior disorder (iRBD), in which people physically act out their dreams, is one of the strongest early warning signs of diseases like Parkinson's. Some theories suggest these diseases may start in the gut and travel to the brain, so the researchers looked at stool samples from 21 people with iRBD and 15 healthy controls. They measured chemicals in the stool and the types of bacteria present. People with iRBD showed signs that gut bacteria were fermenting more protein (higher branched-chain fatty acids and p-cresol) and lower levels of indole and related tryptophan-derived compounds. They also had lower bile acids, higher acylcarnitines, fewer Blautia and Faecalibacterium bacteria, and more Oscillospirales. Combining chemical and bacterial data, a statistical model separated patients from controls with about 85% cross-validated accuracy within this group. This research suggests there may be detectable gut-related differences in iRBD, but the study was small, cross-sectional, and exploratory, so the results are preliminary. It cannot show that gut changes cause disease or predict who will develop Parkinson's or related conditions; larger, long-term studies are needed.
Ascari F, Baldelli L, Scicchitano D, Pellegrini C, Ravaioli F, De Fanti S, et al.. (2026). Exploratory Metabolomic and Metagenomic Profiling of Fecal Samples in Isolated REM Sleep Behavior Disorder.. Biomolecules. https://doi.org/10.3390/biom16101456