When people think of Parkinson’s disease, they might think of Michael J. Fox or tremors, but very few people think of the stomach and intestines.

Up until recently, scientists were also not thinking about the gut in relation to Parkinson’s disease. But today, study upon study is starting to prove that there is a strong link between the two.

And now, research is showing the Parkinson’s disease may actually start entirely in the gut, which raises so many questions and hope for a cure or prevention method.

However, in order to fully understand the importance of this research, let’s first answer a few more basic questions like, “What is Parkinson’s disease?” and “Who does it affect in the United States?”

What is Parkinson’s disease?

According to the Parkinson’s Foundation, Parkinson’s disease is, “a neurodegenerative disorder that affects predominately dopamine-producing (“dopaminergic”) neurons in a specific area of the brain called substantia nigra.”

There is currently no cure for Parkinson’s disease and the cause of the disease is still not fully known.

The symptoms of the disease vary from person to person. In fact, 20% of people with Parkinson’s disease do not experience the most thought-of symptom: a tremor. Symptoms typically develop slowly over time. Other symptoms include: slowness of movement, limb rigidity, gait and balance problems, constipation, changes in speech, and changes in writing.

Parkinson’s disease typically starts showing symptoms at 50 years of age or older. However, young-onset Parkinson’s disease does affect people younger than 50 years old.

There are two categories of Parkinsons. Idiopathic Parkinson’s is the most common form of the disease, affecting approximately 85% of people with the disease.

15% of people with parkinsonian symptoms have one of many diseases termed, atypical parkinsonism disorders. These disorders include Mutliple System Atrophy (MSA), Shy-Drager syndrome, striatonigral degeneration, olivopontecerebellar atrophy, Progressive Supranuclear Palsy (PSP), Corticobasal Syndrome (CBS), Dementia with Lewy bodies (DLB), Drug-induced Parkinsonism, and Vascular Parkinsonism (VP).

Currently, there is no definitive diagnostic test for Parkinson’s disease. Instead, a specialized doctor can diagnose Parkinson’s disease based on medical history, signs and symptoms, and a neurological and physical examination.

Imaging tests such as an MRI, ultrasound of the brain, SPECT, or PET scans are also useful for ruling out other disorders, but are not especially useful for diagnosing Parkinson’s disease.

Treatment for Parkinson’s disease varies from patient to patient. The drug, carbidopa-levodopa, is a medication specifically for Parkinson’s disease and is used to increase levels of dopamine in the brain.

Despite the many unknowns surrounding Parkinson’s disease, there are many people in the United States afflicted with this disease.

Parkinson’s Disease in the United States

Every single year, about 60,000 Americans are diagnosed with Parkinson’s disease resulting in approximately one million people living with Parkinson’s disease in the United States. This is more than people diagnose with multiple sclerosis, muscular dystrophy and Lou Gehrig’s disease combined.

Worldwide, over 10 million people are living with Parkinson’s disease. And men are about 1.5 times more likely to be diagnosed with Parkinson’s disease than women.

Parkinson’s Disease May Start in the Gut

Even though there are so many question marks surrounding Parkinson’s disease, new studies are being released that have given insight as to the cause of Parkinson’s, how to treat it, and how to prevent it.

Scientists are now considering a misfolded protein called alpha-synuclein the possible cause of Parkinson’s disease.

Alpha-synuclein is a naturally occurring protein in everyone’s brain. However, in Parkinson’s patients, the proteins are abnormally folded. When these proteins gather in the brain, they clump up and form Lewy bodies.

In 2005, research was first starting to show that people with Parkinson’s disease not only had clumps of these proteins in their brains, but also in their guts.

Another research study performer late rin 2005 found that people who had ulcers and underwent a vagatomy—a procedure that severs the base of the vagus nerve, which connects the brain to the stomach—had a 40% lower risk of developing Parkinson’s later in life.

Each of these studies made leaps and bounds in scientists’ understanding of how Parkinson’s may start in the gut. However, one question remained: how can these proteins travel from the gut to the brain? As Dr. Rodger Liddle, senior author of a recent study, stated, “nerves are not open in the lumen [or inside of the gastrointestinal tract].”

However, in 2015, research found that cells in the lining of the small intestine were acting a lot like nerve cells. These nerve-like cells were endocrine cells, which produced hormones. And these endocrine cells contained neurotransmitters and other proteins typically found in neurons. In fact, they branched out and communicated similarly to neurons.

So when they were placed near a neuron, they branched out and connected to them. As Liddle described: “It was only afterwards that we started putting these things together — these cells have a lot of nerve-like properties, [so] let’s see if they also contain alpha-synuclein. And if they do, maybe they could be the source of Parkinson’s disease”

The most recent study linking Parkinson’s disease to the gut was published in June of 2017. Charles Bevins, an expert of intestinal immunity at University of California Davis, explained, “The gut-brain immune axis seems to be on a cusp of an explosion of new insights, and this work offers an exceptionally exciting new hypothesis.”

This study performed by researchers at Duke University and University of California, San Francisco demonstrated that the alpha-synuclein proteins are capable of starting in the gut and then traveling to the brain.

“There is abundant evidence that misfolded alpha-synuclein is found in the nerves of the gut before it appears in the brain, but exactly where this misfolding occurs is unknown,” explained gastroenterologist Rodger Liddle, M.D., senior author and professor of medicine at Duke. “This is another piece of evidence that supports the hypothesis that Parkinson’s arises in the gut.”

So what does this mean for the future of our understanding of Parkinson’s disease? If the direct cause of Parkinson’s disease was pinpointed to this specific protein, new therapies could be developed and new prevention methods could possible result in far fewer people living with Parkinson’s disease.

As Liddle said, “Unfortunately, there aren’t great treatments for Parkinson’s disease right now. It’s conceivable down the road that there could be ways to prevent alpha-synuclein misfolding, if you can make the diagnosis early.”