Origins of Parkinson’s may lie in the gut

Origins of Parkinson’s may lie in the gut

October 2, 2023

It has been more than 200 years since the first detailed description of Parkinson’s disease was published in 1817 by British physician James Parkinson. Yet, the disease now bearing his name still has no cure, and why some people get it and others don’t remains a mystery.

“No one really knows what causes Parkinson’s disease, other than about 10 to 20 percent is genetic,” said Ted M. Dawson, a professor of neurology at Johns Hopkins University School of Medicine. “Right now, the only therapies we have are symptomatic. We don’t have anything that slows the progression.”

Researchers such as Dawson have been searching for clues, and in the last two decades, a growing body of evidence points to an unexpected origin for Parkinson’s disease: the gut.

The ‘gut-first’ hypothesis

What is known as the “gut-first”— as opposed to “brain-first” — hypothesis states that Parkinson’s begins as abnormal proteins in the nerves of the gastrointestinal tract. While normal proteins fold into a specific three-dimensional shape, misfolded proteins fail to achieve this form.

Misfolded proteins, found excessively in the post-mortem brains of patients with Parkinson’s as well as Alzheimer’s, accumulate into large, toxic clumps that disrupt nerve cell function.

“According to the hypothesis, the inciting agent — this misfolded protein — starts in the nerves of the gut wall and ascends to the brain, causing those pathological changes that lead to Parkinson’s,” said Pankaj J. Pasricha, gastroenterologist and chair of internal medicine at the Mayo Clinic. “If we can prove that the disease is progressing from the gut to the brain, then we can start thinking about early prevention.”

Gut problems are risk factors for Parkinson’s

The link between Parkinson’s, traditionally considered a brain disorder, and the gastrointestinal tract is not new. Constipation is considered a risk factor for Parkinson’s and one of the most prevalent non-motor symptoms, affecting up to two-thirds of all patients.

A meta-analysis of four population studies found that patients with inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, have a 46 percent greater likelihood of developing Parkinson’s. The seemingly unrelated conditions even share a common genetic mutation. One of the studies also showed that individuals with IBD who received drugs to reduce their gut inflammation had a 78 percent lower incidence of Parkinson’s disease compared with those who did not.

“Symptoms of Parkinson’s related to the gut,” such as constipation and dysphagia, “can present years before more typical signs like tremor, stiffness and difficulty walking,” said Nabila Dahodwala, director of the Parkinson Foundation Center of Excellence at the University of Pennsylvania. “Some people think that means you actually have the disease much earlier — and if that’s the case, we need to rethink how we define Parkinson’s.”

Solving the long-standing mystery of how most cases of Parkinson’s begin — because at least 85 percent of cases are sporadic and not genetic — opens the door for early detection and treatment.

Regardless of which hypothesis is correct, Dahodwala recommends that everyone — not just those at risk for Parkinson’s — should engage in behaviors known to benefit cognitive health, including regular exercise and healthy eating patterns such as the Mediterranean diet, which emphasizes, among other things, grains, vegetables and nuts, and limits red meats and sweets.

Read the full article here:

About The Author:

Meeri Kim is a freelance science writer who has contributed to The Washington Post since 2013. She has a PhD in physics from the University of Pennsylvania.  Twitter

Do you have a question about human behavior or neuroscience? Email and they may answer it in a future column.