Why Bacterial Metabolites Could Be a Biomarker for Parkinson Disease

Researchers sought to analyze bacterial-derived metabolites, particularly TMAO pathway and SCFA, of patients with PD and compare the metabolites with control individuals within their households and patients with MSA.

Bacterial metabolites may be a biomarker of Parkinson disease (PD), according to a study published in Neurobiology of Disease.

The etiopathogenesis of PD is unclear, but it appears to involve several factors. Prior studies have indicated that patients with PD, regardless of treatment history, tend to have different intestinal microbiota compared with age-matched control individuals. Other studies have indicated trimethylamine-N-oxide (TMAO) pathway contributes to age-associated diseases. Few studies have examined TMAO in patients with PD.

In the current study, researchers analyzed the bacterial-derived metabolites, particularly TMAO pathway and short chain fatty acids (SCFA), of patients with PD. They compared the metabolites with control individuals within their population, control individuals within their households, and individuals with multiple system atrophy (MSA).

Compared with population control individuals, patients with PD had higher levels of TMAO pathway constituents, including betaine, butyrobetaine, TMA, and TMAO, independent of medication status, disease characteristics, and lifestyle.

Treated patients with PD tended to have longer disease duration and increased clinical severity compared with patients who were treatment naïve.

TMA was higher in treated patients compared with population control individuals and treatment naïve patients. TMAO was higher among both treatment naïve and treated patients with PD compared with population control individuals.

Treated patients with PD had reduced lactic acid compared with treatment naïve patients.

Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) indicated succinic acid was linked with lower PD and disease severity. Constipation, assessed with PROMIS, increased with succinic acid (P =.01; r=.35, q=.04) and decreased with butyric acid (P <.01; r=-.51, q=.01).

TMA/Butyrate was higher in patients with PD compared with population control individuals (q=0.01).

Treated patients with PD had higher TMA/Butyrate ratios compared with the other groups, and there was a higher ratio of TMA to other SCFA.

This group also had lower MDS-UPDRS scores compared with treated patients with MSA.

Limitations of the study included small sample size.

The researchers said bacterial-derived metabolites could be a biomarker of disease and modifications of the microbiota could be a treatment approach for PD.

“Additional studies to understand the potential of TMAO and other bacterial metabolites to serve as a biomarker or therapeutic targets are warranted,” they concluded.

Disclosure: One study author declared affiliations with biotech/pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Voigt RM, Wang Z, Brown JM, et al. Gut microbial metabolites in Parkinson’s disease: Association with lifestyle, disease characteristics, and treatment status. Neurobiology of Disease. Published online June 2, 2022. doi: 10.1016/j.nbd.2022.105780