Originally published 2017-06-23.
There is growing evidence that, in at least some people, Parkinson’s disease may begin in the gut years before it reaches the brain. One of the most cited pieces of that evidence is a 2017 Swedish study published in the journal Neurology. It found that people who had a full (truncal) vagotomy, an operation that cuts the main vagus nerve between the stomach and the brain, were about 40 percent less likely to develop Parkinson’s at least five years later than people in the general population. The finding supports the gut-origin idea but does not prove it, and it does not mean every case starts in the gut.
Below is what the study did, why the vagus nerve matters, what other research has added since, and what it does and does not mean for patients.
Why scientists suspect the gut
Parkinson’s is best known for its movement symptoms: tremor, stiffness, slowness and problems with balance. These appear when dopamine-producing nerve cells in a brain region called the substantia nigra die off. Inside affected cells, a protein called alpha-synuclein folds into the wrong shape and clumps together, forming deposits known as Lewy bodies.
Long before movement problems show up, many people have quieter warning signs. Constipation is one of the most common, and it can begin decades before diagnosis. A reduced sense of smell and acting out dreams during sleep are others. That timeline made researchers wonder whether the disease process might start outside the brain.
In 2003 the German neuroanatomist Heiko Braak and colleagues proposed that something, perhaps a pathogen or toxin, might enter through the nose or the digestive tract and trigger the misfolding of alpha-synuclein there. The faulty protein could then travel along nerves into the brainstem and, over years, climb up to the regions that control movement. The first brain area Braak saw affected was the base of the vagus nerve in the lower brainstem, which pointed straight at the gut.
What the vagus nerve does
The vagus nerve is the longest of the cranial nerves. It runs from the brainstem down through the neck and chest into the abdomen, carrying signals in both directions. It helps regulate heart rate, breathing and digestion without any conscious effort, and it is one of the main lines of communication in what scientists call the gut-brain axis.
A vagotomy is surgery that cuts the vagus nerve or some of its branches. It was once a common treatment for stomach ulcers because it reduces acid production. There are two main types:
- Truncal vagotomy cuts the main trunks of the nerve, removing most of its connection to the digestive organs.
- Selective vagotomy cuts only the branches that serve parts of the stomach, leaving the rest intact.
The operation is rare today. Once doctors learned that most ulcers are caused by the bacterium Helicobacter pylori, and once powerful acid-reducing drugs became available, the need for ulcer surgery fell sharply. That history is what made the Swedish study possible: decades of records from a time when vagotomy was routine.
The 2017 Swedish registry study
A team led by Bojing Liu at the Karolinska Institutet in Stockholm used Swedish national health registers covering about 40 years. They identified 9,430 people who had a vagotomy and compared them with 377,200 people from the general population who had not.
When all vagotomies were lumped together, the difference was small and not statistically significant: 1.07 percent of the surgery group developed Parkinson’s, against 1.28 percent of the comparison group. The picture changed when the researchers split the operations by type and looked at people followed for at least five years.
- After a truncal vagotomy, 19 people developed Parkinson’s, or 0.78 percent.
- After a selective vagotomy, 60 people developed it, or 1.08 percent.
- Among people with no surgery followed for at least five years, 3,932 developed it, or 1.15 percent.
After adjusting for other health conditions such as diabetes, chronic lung disease and arthritis, people with a truncal vagotomy at least five years earlier had about a 40 percent lower risk. A selective vagotomy, which leaves most of the nerve in place, did not show the same protective pattern. That contrast is what makes the result interesting: if a faulty protein travels from gut to brain along the vagus nerve, cutting the whole nerve should block the route, while cutting only part of it should help much less.
Liu summarised the finding carefully:
“These results provide preliminary evidence that Parkinson’s disease may start in the gut.”
Limits of the evidence
The numbers in the truncal group were small, only 19 cases, which makes the estimate less certain. The registers also lacked information on some important risk factors. Smoking and coffee drinking are both linked to lower Parkinson’s risk in population studies, and genetics plays a role in some families; none of these could be fully accounted for.
A Danish registry study published in 2015 had reported a similar pattern, but a later reanalysis of Danish data questioned it, so the findings are not entirely consistent. And like all observational research, these studies show an association rather than proof of cause.
Finally, Parkinson’s is now often described as a syndrome: a shared set of symptoms that may arise through more than one route. Liu also noted that there may be multiple causes and pathways. Many researchers today talk about possible “body-first” and “brain-first” forms of the disease, with the gut route explaining only some cases.
One small correction to the way this research is often retold: the misfolding of alpha-synuclein is a change in a protein’s shape, not a genetic mistake. Genes can raise the risk, but the spreading “mistake” in this theory is the protein itself.
What other research has added
The Swedish study was part of a wider wave of work on the gut and Parkinson’s:
- Gut bacteria in mice (2016). Researchers at Caltech reported in the journal Cell that mice genetically prone to a Parkinson’s-like condition developed fewer motor problems when raised germ-free, and worse ones when given gut bacteria from people with Parkinson’s.
- Gut bacteria in people (2017). A US study published in Movement Disorders found differences in the gut microbiome of people with Parkinson’s compared with people without it, adding to similar findings from Finland and elsewhere.
- Tracking the protein (2019). A Johns Hopkins team injected misfolded alpha-synuclein into the gut walls of mice and showed that it spread to the brain over months; cutting the vagus nerve stopped that spread.
Animal experiments do not translate directly to humans, and microbiome studies cannot yet say whether gut changes are a cause or a consequence of the disease. Still, the different lines of evidence point in a broadly consistent direction.
What this means for patients and families
None of this research suggests that anyone should have nerve surgery to prevent Parkinson’s. Vagotomy has real side effects on digestion, and only a small share of people would ever develop the disease anyway. The value of the work lies elsewhere: if the disease does begin in the gut for some people, there may one day be a chance to detect it earlier, perhaps through gut tissue or stool tests, and to intervene before the brain is badly affected.
For now, there is no proven way to prevent Parkinson’s, and current treatments, such as levodopa and deep brain stimulation, ease symptoms rather than stop the disease. Constipation on its own is extremely common and usually has nothing to do with Parkinson’s. If you are worried about new symptoms such as a tremor, stiffness or changes in your sense of smell, talk to a doctor.
The bottom line
The 2017 study found that cutting the whole vagus nerve was linked to a lower chance of Parkinson’s years later, which fits the idea that the disease can travel from gut to brain. It was preliminary, based on small numbers, and could not rule out other explanations. Combined with the animal and microbiome research since, it has helped make the gut one of the most active areas in the search for Parkinson’s causes.
Sources: Liu B. et al., “Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study,” Neurology (2017); American Academy of Neurology news release via Newswise; Wikipedia: Vagotomy; Wikipedia: Braak staging; Wikipedia: Parkinson’s disease; The Lancet Neurology; ScienceAlert.
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