Imagine wearing oven mitts while you brush your teeth: this is how one 70-year-old woman described the experience of having Parkinson’s disease (PD). More than 10 million people worldwide suffer from this progressive neurological condition characterized by tremors, muscle stiffness, and slowness of movement. Because of the changes in motor function, PD makes everyday tasks—from personal hygiene to texting—more difficult.
Parkinson’s is certainly a disease of the brain, since scientists know it involves the death of specific neurons that produce a chemical messenger called dopamine. But intriguingly, more and more research is connecting the disease with what goes on in the digestive tract—including the gut microbiota.
Filip Scheperjans of Helsinki University Hospital (Finland), a neurologist and leading researcher on PD and gut microbiota, tells GMFH there are several reasons to think PD may be related in some way to the gut.
“Patients suffer from a broad spectrum of gastrointestinal symptoms,” says Scheperjans. That is, he and other physicians have documented that PD and gastrointestinal problems go hand in hand—with constipation, for example, often appearing years before the onset of motor symptoms.
Not only that, says Scheperjans—”In the gastrointestinal tract of PD patients, similar neuropathological changes have been described as in the brain.” The mis-folded protein (alpha-synuclein) that is found in the brains of those with PD has also been identified in patients’ intestines (more specifically: in the enteric nervous system of the gut) even before the neurodegeneration is advanced enough to affect movement. This leads researchers to think the protein could somehow be involved in causing the disease.
Research from Scheperjans’ team found gut microbiota changes in those with PD, which correlated with their motor symptoms: as a group of bacteria called Enterobacteriaceae increased, so did the severity of postural instability and gait difficulty. Other studies have indeed found PD-associated changes in gut microbiota, but the species that ‘mark’ PD are different from study to study.
Since those with PD experience changes in oral saliva production and a decreased sense of smell, Scheperjans also recently investigated the microbiota of the mouth and nose in those with PD.
“We were interested in whether microbiota would also be changed in the nasal and oral cavities in PD patients, and could be useful as a biomarker,” he explains.
He and his colleagues saw significant differences in the oral microbiome—but not the nasal microbiome—in people with PD compared to healthy individuals. The groups of bacteria that were increased in individuals with PD included a number of possible opportunistic pathogens.
“Interestingly, we found that Prevotella genus was increased in the mouth[s] of PD subjects and it is considered a potential pathogen there, related to periodontal disease,” says Scheperjans. “The same genus was decreased in the gut of PD patients.” He explains that this is not necessarily a contradiction, since the same bacteria could have different jobs in the environment of the mouth compared to the (oxygen-free) gut. Moreover, different sub-groups of Prevotella can have remarkably different functions and physiological effects despite their shared genus name.
Another line of research on the gut and PD has focused on the vagus nerve, the cranial nerve extending from the abdomen to the brainstem, responsible for controlling unconscious body processes like gut motility, food digestion, and heart rate. Some think the vagus nerve could be how the abnormal alpha-synuclein protein is transported to the brainstem.
A team of researchers from the Karolinska Institute in Stockholm (Sweden) recently studied national registers to find people who had undergone a vagotomy—a surgical procedure in which either the main trunk or branches of the vagus nerve are removed. Vagotomy is an outdated procedure, typically performed before 1980, to block acid secretion in patients with recurrent gastric or duodenal ulcers. The researchers found that, over four decades, just 1% of the people with a vagotomy developed PD, compared with 1.28% of other individuals; specifically, those who had undergone a truncal vagotomy (one type of vagotomy that involves the full resection of the main trunk of the vagus nerve) tended to have a lower rate of developing the disease. The difference between the groups was not significant—so the interactions are probably complex—but the data did not rule out a gut-PD connection.
How could all these pieces fit together? According to Scheperjans, we don’t have the answers yet, but an early theory is forming. “There is one hypothesis that gut microbiota could be related to colonic inflammation and neuropathology in early stages of PD,” he explains. A recent review article described it like this: something in the environment could trigger an immune response in the gut that affected gut microbiota and led to the observed alpha-synuclein abnormalities. In turn, this abnormal protein could exacerbate inflammation and could travel from the gut to the brain via the vagus nerve. Concurrently, sustained inflammation in the intestine could promote systemic inflammation—which may or may not involve an abnormal oral microbiota—eventually leading to the neurodegeneration of PD.
To bring clarity to what really causes this complex, multi-system disorder, many years of research lie ahead. But it’s safe to say the gut is a player in PD—with the gut microbiota possibly providing scientists with a rich source of clues.
Houser & Tansey. The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? npj Parkinson’s Disease. 2017; 3.
Liu B, Fang F, Pedersen NL, et al. Vagotomy and Parkinson disease: A Swedish register–based matched-cohort study. Neurology. 2017; 88(21): 1996-2002. DOI: 10.1212/WNL.0000000000003961
Pereira PAB, Velma TEA, Paulin L, Pekkonen E, Auvinen P, Scheperjans F. Oral and nasal microbiota in Parkinson’s disease. Parkinsonism and Related Disorders. 2017; 38: 61–67.
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