By Harini Sarva, MD

Assistant Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Sarva reports she is a consultant for Acorda Therapeutics, Amneal Pharmaceuticals, and Merz Pharma.

SYNOPSIS: Certain risk factors and prodromal markers of Parkinson’s disease (PD), such as constipation and rapid eye movement sleep behavior disorder, are associated with specific bacterial compositions of the gut. However, the value of gut microbiome data to predict the risk of PD development needs further investigation.

SOURCE: Heinzel S, Aho VT, Suenkel U, et al. Gut microbiome signatures of risk and prodromal markers of Parkinson’s disease. Ann Neurol 2020;88:320-331.

Stool samples were obtained from 745 participants of the Tubingen Evaluation of Risk Factors for Early Detection of Neurodegeneration (TREND) study. Participants were chosen based on the presence of olfactory loss, depression, and/or possible rapid eye movement (REM) sleep behavior disorder (RBD), all of which increase the risk of Parkinson’s disease (PD) development based on criteria established by the International Parkinson’s Disease and Movement Disorders Society. Nine risk factors (male gender, diabetes, and smoking, among others) and nine prodromal factors (constipation, depression, RBD, and olfactory loss) based on the new criteria were chosen for evaluation of possible association with gut microbiota. Of the 745 samples, 666 were included for analysis. DNA analysis and microbial measures of diversity were performed. The mean age of the sample population was approximately 68 years, the majority were men, one-quarter performed no physical activity, and approximately 13% had RBD. The most common bacteria found in the stool samples included Bacteroides, followed by Faecalibacterium, Gemmiger, Roseburia, Prevotella, and Ruminococcus. Constipation severity and age were positively associated with the alpha-diversity or abundance of a genus in the gut. The intersample differences in microbial composition, as demonstrated by beta-diversity, age, physical activity, body mass index, and constipation, had the greatest effect on variance.

Certain risk factors were associated with bacterial enterotypes. For example, the lowest physical activity levels and severe constipation were associated with Firmicutes enterotype, but high physical activity level was associated with Bacteroides. Certain factors were associated with lower abundance of bacterial species; for example, severe constipation was connected to fewer Faecalibacterium.

COMMENTARY

Alpha-synuclein pathology is present in the gut in patients with PD, and alterations in the gut microbiome leading to increased inflammation have been well described. This study demonstrated that certain risk factors and prodromal markers of PD were associated with different compositions of gut bacterial species. Although constipation, RBD, smoking, and subthreshold parkinsonism were more commonly associated with microbial changes, other factors, such as substantia nigra hypoechogenicity, orthostatic hypotension, family history of PD, and olfactory loss, did not demonstrate any associations.

However, it is unclear how these microbial associations affect prodromal PD. Medications, lifestyle choices such as diet and exercise, and the presence of other chronic conditions can complicate bowel function, microbial composition, and the diversity of the microbiome.

Further confirmation of these findings may allow us to distinguish between those with and without PD and potentially help predict risk when combining stool samples with already established prodromal markers. With more data about the gut microbiome, this advancing research field may help us predict disease severity of PD patients and to customize drug therapies.