Short-Chain Fatty Acid-Producing Gut Microbiota Is Decreased in Parkinson’s Disease but Not in Rapid-Eye-Movement Sleep Behavior Disorder Original paper

What was studied?

This study examined the gut microbiota composition in patients with idiopathic rapid-eye-movement sleep behavior disorder (iRBD)—a prodromal condition with a high risk for developing Parkinson’s disease (PD) and compared it to healthy controls and individuals with PD. Using 16S rRNA gene sequencing, gut microbiota from 26 Japanese iRBD patients and 137 controls were analyzed; further, a meta-analysis incorporated a German iRBD cohort and PD data from five countries. The research aimed to identify taxonomic changes in gut bacteria, focusing on short-chain fatty acid (SCFA)-producing microbiota, and to distinguish microbiome signatures characteristic of iRBD and PD. Advanced clustering methods (including LIGER, a topic modeling approach) were used to define enterotypes and trace microbiome shifts across disease states, with a particular emphasis on genera known for mucin degradation (such as Akkermansia) and SCFA production (such as Faecalibacterium and Roseburia).

Who was studied?

The primary Japanese cohort included 26 patients with iRBD, diagnosed by established sleep disorder criteria, and 137 age-matched healthy controls recruited from four hospitals. Patients with significant comorbidities (e.g., diabetes, malignancies, autoimmune diseases) or recent antibiotic use were excluded. The meta-analysis also included a German iRBD cohort (20 iRBD patients, 38 controls) and PD cohorts previously studied across Japan, USA, Finland, Russia, and Germany (totaling 223 PD patients). Demographic and lifestyle factors (age, sex, BMI, constipation, diet, medication use) were carefully recorded and controlled for in statistical analyses to reduce confounding.

Most important findings

A central finding was that the gut microbiota of iRBD patients, while distinct from healthy controls, does not exhibit the same degree of dysbiosis seen in PD, particularly regarding SCFA-producing bacteria. In both Japanese and German iRBD cohorts, there was a consistent increase in the mucin-degrading genus Akkermansia and its parent family Akkermansiaceae. However, the abundance of key SCFA-producing genera—Faecalibacterium, Roseburia, and Lachnospiraceae ND3007 group—was not significantly reduced in iRBD, contrasting with their marked depletion in PD patients across five countries. Clustering analysis revealed a shift in enterotypes from controls (enriched in SCFA producers) to PD (enriched in non-SCFA producers), with iRBD patients intermediate but closer to controls. Gradual increases in Akkermansia and decreases in SCFA-producers tracked with the progression from control to iRBD to PD, suggesting a stepwise microbiome evolution during disease development.

Key implications

This study suggests that increased Akkermansia—implicated in mucin layer degradation and increased gut permeability—is an early, prodromal microbiome signature, appearing at the iRBD stage prior to overt PD. In contrast, loss of SCFA-producing bacteria appears to be a later event, closely tied to PD onset and progression. Since SCFAs are linked to anti-inflammatory regulatory T cell induction, their decline may be a prerequisite for neurodegeneration in PD. These findings clarify the temporal sequence of gut microbiome alterations in synucleinopathy and highlight Akkermansia as a potential early biomarker, while underscoring the therapeutic potential of prebiotic and probiotic interventions aimed at bolstering SCFA-producing bacteria and mucin layer integrity to possibly delay or prevent PD.

Citation

Nishiwaki H, Hamaguchi T, Ito M, Ishida T, Maeda T, Kashihara K, Tsuboi Y, Ueyama J, Shimamura T, Mori H, Kurokawa K, Katsuno M, Hirayama M, Ohno K. Short-chain fatty acid-producing gut microbiota is decreased in Parkinson’s disease but not in rapid-eye-movement sleep behavior disorder. mSystems. 2020;5(6):e00797-20. doi:10.1128/mSystems.00797-20