Does Parkinson’s Disease Begin in the Gut?
Every nine minutes, someone in the United States is diagnosed with Parkinson’s disease, one of the most common neurodegenerative disorders associated with aging. Because as many as one in five Americans will reach the age of 65 or older by 2030, health care workers are bracing for a growing epidemic of these debilitating and incurable conditions. Now new Yale research suggests that several of these diseases may originate not in the nervous system, but in the gut.
As accumulating experimental evidence advances our understanding of the apparent connection between alterations in the microbiome and disorders originally thought to be exclusively of the nervous system, Yale researchers are seeking to understand the role of the gut-brain axis. Among these researchers are David Hafler, MD, chair and William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology, and Noah Palm, PhD, assistant professor of immunobiology, who have received support from the Aligning Sciences Across Parkinson’s (ASAP) initiative to better understand the core etiology of the disease.
“The old saying, ‘You are what you eat,’ may have more meaning than we previously thought,” says Hafler.
“All of this research is part of the next generation of the most exciting immunological discoveries,” says Palm.
What is known about the gut-brain connection to neurodegenerative conditions?
How signals from the gut influence the brain has fascinated and intrigued researchers. There have been three main hypotheses about the pathways involved.
First, emerging research in immunology over the past decade—much of which has been conducted at Yale, including by Ruslan Medzhitov, PhD, Sterling Professor of Immunobiology—has shown that the immune system has significant functions beyond simply fighting infection, including tissue regulation and cellular homeostasis. Some researchers postulated that motile immune cells in the gut are programmed to move to places they’re needed within the body to fulfill these purposes. Some of these immune cells might be homing in on the brain. Andrew Wang, MD, PhD, assistant professor of medicine and of immunobiology and Hafler are investigating how T cells migrate from the gut to the brain, both in healthy individuals and in experimental animals to better understand the role of the immune system in nervous system homeostasis.
Second, scientists believed that the microbiome could influence the brain through the neuronal circuitry that links the gut to the brain via the vagus nerve, which acts as a “superhighway” between our organs and the central nervous system, says Palm.
And finally, researchers hypothesized that the connection could be due to chemical communication through metabolites—small molecules made by the microbiome to break down food, drugs, and other natural and synthesized substances.
“It turns out that over the past five to 10 years all of these possible pathways have proven to be true in one shape or another,” says Palm.
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