Identifying early-stage Parkinson's

Research shows link between Parkinson's disease and the microbiome that could aid in diagnosis

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SYRACUSE, N.Y.—Even with diseases for which we have no cures, early detection of a disorder is often key to better quality of life and slower decline of function—and neurological ailments like Parkinson’s disease (PD) and Alzheimer’s disease clearly fit this bill.
And in a sign of diagnostic hope related to PD, recent research published under the title “The oral microbiome of early stage Parkinson’s disease and its relationship with functional measures of motor and non-motor function” in the journal PLOS One indicates that a simple saliva swab may provide an accurate way of detecting PD in its earliest stage.
Also, as has been the case with a number of research breakthroughs and new lines of research inquiry lately, the human microbiome is at the heart of it.
In the paper, researchers from Upstate Medical University and Quadrant Biosciences Inc., a StartUp NY company based at Upstate Medical University, discovered that specific bacteria in the oral microbiome accurately differentiate early-stage Parkinson’s disease (esPD) from healthy controls.
As the university noted in a news posting on their website, “Moreover, these changes in individuals with esPD appeared to be related to neural and brain function. The results of the study suggest that the oral microbiome may represent an easily accessible and informative microenvironment that offers new insights into Parkinson’s disease.”
“The major impetus behind our efforts is the earliest possible detection of Parkinson’s disease before the onset of motor symptoms. That is the Holy Grail that we all chase,” said Dr. Frank Middleton, an Upstate Medical University associate professor of neuroscience and physiology and one of the principal authors of the research.
This isn’t the first time anyone has noted changes in the function and microbiome of the upper and lower gastrointestinal (GI) tract with regard to PD, but studies have tended to focus on the fecal microbiome, as well focusing mostly on more advanced PD. So, with this study—which is the first in a series of planned studies to evaluate the importance of the oral microbiome in esPD—the focus on early disease state and the oral microbiome were definite differentiators.
Using next-generation sequencing technology, the researchers quantified the complete composition of microbes (including bacteria, yeast, phages and viruses) in the saliva of 48 esPD subjects and 36 age and gender-matched healthy control subjects. In addition to the collection of saliva samples, detailed assessments of motor, cognitive, balance, smell and taste functions were conducted to determine the disease stage.
Significant differences in the composition of the oral microbiome between the esPD and healthy control subjects were observed at an overall accuracy of 84.5 percent, suggesting potentially strong utility as a diagnostic tool. Most of the differences were found in bacterial species abundance, though differences in some species of yeast were also observed. The researchers also found significant changes in a set of nine human or host mRNAs in the saliva, several of which mapped to various brain functions and showed correlations with some of the significantly changed microbial taxa. Finally, significant correlations between many of the microbiota and functional measures were also observed, including those reflecting cognition, balance and disease duration.
The study also suggested that the oral microbiome is not only a robust and reliable source of biological information about PD, but likely a better source than the lower GI tract for identifying changes in microbial abundance.
Noted Middleton: “To date, the vast majority of studies have focused on the fecal microbiome. However, the lower GI tract may be affected by such things as constipation and motility issues, which are common in Parkinson’s disease, or the use of antacids, both of which could influence the environment of the lower GI and potentially give rise to misleading results. By focusing on the beginning of the GI tract, we are largely avoiding changes in the environmental conditions in which the bacteria grow.”
Also, as the authors noted in the paper’s abstract, “Nearly half of our findings were consistent with prior studies in the field obtained through profiling of fecal samples, with others representing highly novel candidates for detection of early stage PD.”
Interestingly, the researchers also pointed out in their paper that not all bacteria found in the oral microbiome of esPD patients appear to be beneficial as they might be in non-diseased individuals.
“Generally regarded as ‘probiotic’ in nature, bacteria within the Bifidobacteriaceae family are proposed to have anti-inflammatory properties and potentially serve beneficial purposes," the authors reported. "Thus, it is possible that the changes we and other groups have seen may reflect a compensatory mechanism in the GI tract. However, while Lactobacilli are also generally considered probiotic, some members of the Lactobacillaceae family may exert a disease-worsening effect in PD. Specifically, Lactobacillus reuteri, which we found significantly increased in our PD subjects, was shown in a prior study to increase alpha-synuclein release in cultured ENS neurons, presumably due to increased firing of mesenteric afferent nerve bundles (caused by decreasing calcium-dependent potassium channel opening and reducing the slow afterhyperpolarization in these neurons).”

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