made her skeptical that Parkinson’s, which affects
half a million people in the United States, was just
a malfunction in the brain.
“I had an initial hunch that food and food quality was part of the issue,” she says. If something in
the environment triggered Parkinson’s, as some
theories suggest, it made sense to her that the
disease would involve the digestive system. Every
time we eat and drink, our insides encounter the
John’s disease progressed slowly and Carlin
kept up her research. In 2015, she found a paper
titled, “Gut microbiota are related to Parkinson’s
disease and clinical phenotype.” The study, by
neurologist Filip Scheperjans of the University
of Helsinki, asked two simple questions: Are
the microorganisms that populate the guts of
Parkinson’s patients different than those of
healthy people? And if so, does that difference
correlate with the stooped posture and difficulty
walking that people with the disorder experience?
Scheperjans’ answer to both questions was yes.
Carlin had picked up on a thread from one of the
newest areas of Parkinson’s research: the relationship between Parkinson’s and the gut. Other than
a small fraction of cases that are inherited, the
cause of Parkinson’s disease is unknown. What is
known is that something kills certain nerve cells,
or neurons, in the brain. Abnormally misfolded
and clumped proteins are the prime suspect.
Some theories suggest a possible role for head
trauma or exposure to heavy metals, pesticides
or air pollution.
People with Parkinson’s often have digestive
issues, such as constipation, long before the disease appears. Since the early 2000s, scientists
have been gathering evidence that the malformed
proteins in the brains of Parkinson’s patients might
actually first appear in the gut or nose (people
with Parkinson’s also commonly lose their sense
From there, the theory goes, these proteins
work their way into the nervous system. Scientists
don’t know exactly where in the gut the misfolded
proteins come from, or why they form, but some
early evidence points to the body’s internal microbial ecosystem. In the latest salvo, scientists from
Sweden reported in October that people who
had their appendix removed had a lower risk of
Parkinson’s years later (SN: 11/24/18, p. 7). The job
of the appendix, which is attached to the colon, is a
bit of a mystery. But the organ may play an important role in intestinal health.
If the gut connection theory proves true — still
a big if — it could open up new avenues to one day
treat or at least slow the disease.
“It really changes the concept of what we consider Parkinson’s,” Scheperjans says. Maybe
Parkinson’s isn’t a brain disease that affects the
gut. Perhaps, for many people, it’s a gut disease
that affects the brain.
London physician James Parkinson wrote “An
essay on the shaking palsy” in 1817, describing six
patients with unexplained tremors. Some also
had digestive problems. (“Action of the bowels
had been very much retarded,” he reported of
one man.) He treated two people with calomel — a
toxic, mercury-based laxative of the time — and
noted that their tremors subsided.
But the digestive idiosyncrasies of the disease
that later bore Parkinson’s name largely faded into
the background for the next two centuries, until
neuroanatomists Heiko Braak and Kelly Del
Tredici, now at the University of Ulm in Germany,
proposed that Parkinson’s disease might arise
from the intestine. Writing in Neurobiology of
Aging in 2003, they and their colleagues based
their theory on autopsies of Parkinson’s patients.
Road to the brain
One theory suggests
that substances swallowed or sniffed set
off an inflammatory
reaction that alters the
gut microbiome. In turn,
proteins called alpha-synuclein may become
misfolded and travel
along the vagus nerve,
from the lining of the
gut to the brain, causing
nerve cell death.
SOURCES: N. TI TOVA E T AL/ NPJ
PARKINSONS DISEASE 2018; R. P.
FRIEDLAND AND M.R. CHAPMAN/
PLOS PATHOGENS 2017