A saliva test may help diagnose Parkinson’s and assess disease severity, according to a recent study.
Biomarkers that reflect problems in the production of energy, with nerve cell messengers, and in gut microflora — each easily detected in saliva — may all contribute to the metabolic changes associated with Parkinson’s disease (PD), the study found.
Titled “Quantitative metabolomics of saliva using proton NMR spectroscopy in patients with Parkinson’s disease and healthy controls,” the study was published in the journal Neurological Sciences.
Because Parkinson’s symptoms are similar to and can be mistaken with those of other neurodegenerative diseases, a precise and early diagnosis can prove challenging. As such, there is a need to identify potential biomarkers that can aid in the diagnosis, understanding, and treatment of this disease.
Changes in metabolism related to energy, neurotransmitters, and oxidative stress — cellular damage as a consequence of high levels of oxidant molecules — have been associated with Parkinson’s. A person’s metabolism involves natural reactions occurring within cells to produce energy and all the necessary compounds for growth, survival, and function.
Prior studies have looked at a few metabolites — any of the intermediate products of metabolic reactions — present in the blood or cerebrospinal fluid (CSF), the liquid surrounding the brain and spinal cord.
Now, researchers from the All India Institute of Medical Sciences in New Delhi wanted to track down possible disease biomarkers present in saliva to further understand the metabolic pathways involved in Parkinson’s.
Testing saliva is a painless, non-invasive, cost-effective, simple, and safe method of investigation, the researchers noted.
The volume and composition of saliva are regulated by a branch of the nervous system controlled by the brain. In addition to molecules unique to saliva, this biologic fluid also carries molecules present in the blood, which together may reflect the presence and stage of disease.
As such, “the analysis of saliva may provide valuable information even at early stages of PD,” the researchers said.
The team collected saliva samples from 76 patients with Parkinson’s, ages 33 to 68, and 37 healthy people (controls). They then applied a powerful technique — called Nuclear Magnetic Resonance (NMR) spectroscopy — to run metabolic profiling to determine the types of metabolites and their concentration in the saliva samples, and to spot potential biomarkers.
The levels of 15 metabolites were significantly increased in patients’ samples compared with those of controls. Specifically, these were: phenylalanine, tyrosine, histidine, glycine, acetoacetate, trimethylamine-N-oxide (TMAO), gammaaminobutyric acid (GABA), N-acetylglutamate (NAG), acetoin, acetate, alanine, fucose, propionate, isoleucine, and valine.
Alterations in histidine, tyrosine, and phenylalanine reflect alterations in neurotransmitters — chemical messengers that allow nerve cells to communicate. Changes in these molecules specifically flag alterations in the production of the neurotransmitter dopamine, whose loss in certain regions of the brain is a hallmark of Parkinson’s.
To understand whether metabolic changes correlated with Parkinson’s disease stages, an additional analysis was done in which patients were divided into two groups. One group, comprising 52 people, were individuals in the early stages of disease (Hoehn and Yahr scale stages 1–2). The other group, with 24 patients, was composed of those with advanced Parkinson’s (Hoehn and Yahr scale stages 2.5 – 3). The Hoehn and Yahr scale, known as H&Y, is an instrument used to measure symptoms’ severity in Parkinson’s.
Contrary to patients in advanced stages, those with early disease had greater saliva concentrations of propionate, valine, acetoin, TMAO, tyrosine, histidine, isoleucine, glycine, GABA, and N-acetylglutamate, when compared with healthy subjects.
“These features may highlight the characteristic changes in metabolite levels during the onset of PD,” the researchers said. They added that a less pronounced concentration of such markers in patients at more advanced stages may be related to their use of dopaminergic therapy (dopamine agonists).
The metabolic profile of the participants’ saliva also correlated with disease duration. A higher concentration of propionate and acetoin correlated with longer disease duration, with lesser amounts of these metabolites correlating to shorter disease duration.
“Acetate and propionate are intestinal microbial metabolites that influence the formation of gut microbiota and the host metabolome [all metabolites present within an organism],” the researchers noted.
In recent years, data has emerged that suggests an association between the gut and the development of Parkinson’s disease. It is believed that gut microbiota may control brain development and behavior through these metabolites. Therefore, imbalances in this environment in response to the loss of dopaminergic neurons may impact both the enteric nervous system — the network of nerves that innervate the gastrointestinal tract — and the central nervous system.
“Motor and gastrointestinal dysfunctions may be associated with the involvement of the enteric nervous system (ENS) in the pathological progression of PD towards the CNS or vice versa,” the researchers said.
The new data from this study reveal potential salivary biomarkers of Parkinson’s disease and pinpoint metabolic pathways deranged by the disease, the researchers said. Such pathways include those involved in the metabolism of amino acids (the building blocks of proteins), energy, neurotransmitters, alterations in the gut microflora, or microbial communities that live in the body’s gastrointestinal tract.
“The results also suggest that symptoms of impaired metabolism may help diagnose PD and assess disease severity,” the team said, noting that larger studies are needed to confirm the link between salivary metabolic profiling and clinical features.