The Gut–Brain Axis in Parkinson’s Disease

Parkinson’s disease (PD) is widely known for its movement-related symptoms such as
tremor, slowness, and stiffness. These result from the loss of dopamine-producing neurons
in the brain. But recent research has shifted attention beyond the brain, pointing to the gut
as a possible early site of disease onset. Increasingly, studies show that gastrointestinal (GI)
issues may not only accompany PD but actually precede it, sometimes by decades, raising
the possibility of a gut-origin theory for the disease.

This theory is most prominently supported by Braak’s Hypothesis, which proposes that
misfolded alpha-synuclein, key protein involved in PD, first appears in the enteric nervous
system (ENS), the vast network of neurons that controls gut function. From there, it may
spread to the brain via the vagus nerve in a prion-like fashion. This idea is supported by
several lines of evidence, including the early appearance of GI symptoms and the detection
of alpha-synuclein aggregates in gut tissues years before a PD diagnosis.

A recent nationwide study by Konings et al. (2023) adds strong statistical backing to this idea.
Using a large electronic health record database, the researchers identified several GI
conditions that consistently occur more often in people who later develop PD. These include
constipation, dysphagia (difficulty swallowing), gastroparesis (delayed stomach emptying),
and irritable bowel syndrome (IBS) without diarrhoea. Unlike in other brain diseases such as
Alzheimer’s or stroke, these GI symptoms were particularly associated with Parkinson’s.
Constipation, for example, was found to increase the risk of PD diagnosis by more than two-
fold, and dysphagia—typically thought of as a late-stage symptom—was shown to appear
much earlier than previously believed.

Meanwhile, Yemula et al. (2021) explored the role of the gut microbiome—the trillions of
bacteria and microbes in our intestines—in Parkinson’s disease. Their review points to a
pattern of dysbiosis, or microbial imbalance, in PD patients. In particular, reductions in
beneficial, anti-inflammatory bacteria such as Prevotella, Coprococcus, and Blautia have
been observed. These microbes typically produce short-chain fatty acids (SCFAs), like
butyrate, which help maintain gut barrier integrity and reduce inflammation. In contrast,

levels of potentially harmful, pro-inflammatory bacteria such as Enterobacteriaceae,
Akkermansia, and Lactobacillus tend to be increased in PD.
This shift in microbial populations may lead to a “leaky gut,” where the gut lining becomes
more permeable. Harmful substances can then enter the bloodstream and potentially reach
the brain, where they may trigger microglial activation. Microglia are the brain’s immune cells,
and while they normally protect neurons, prolonged overactivation can cause inflammation
and neuronal damage, potentially contributing to PD progression.

Diet may play a key role in shaping the gut microbiota and influencing PD risk. Yemula and
colleagues highlight that caffeine, polyphenols (from tea and berries), omega-3 fatty acids,
and vitamins B6, C, D, and E are associated with reduced risk. The Mediterranean diet, rich
in fiber, healthy fats, and antioxidants, appears particularly beneficial. On the other hand,
high intake of dairy and animal fat may increase PD risk, possibly through inflammatory
mechanisms.

Diet also influences the effectiveness of levodopa (L-dopa), the main medication used to
treat PD. High-protein meals can compete with L-dopa for absorption in the gut and across
the blood–brain barrier, potentially reducing its effectiveness. Adjusting diet, such as by
lowering protein intake or timing meals, can improve symptom control in some patients.
Other potential risk modifiers include appendectomy (removal of the appendix), which some
studies, including Konings et al., suggest may reduce PD risk. The appendix may serve as a
reservoir for misfolded alpha-synuclein or pro-inflammatory bacteria, though findings
remain inconclusive after statistical correction. Vagotomy (cutting the vagus nerve) was also
not found to be protective in the latest study, though earlier evidence suggested it might
block the gut-to-brain spread of pathology.

Together, these findings paint a more complex picture of Parkinson’s disease—one in which
the gut may play a central role in both its origin and progression. Recognizing GI symptoms
such as constipation, gastroparesis, and dysphagia as possible early warning signs opens
up new opportunities for earlier diagnosis. Meanwhile, modulating the gut microbiome through diet or microbiota-targeted therapies could offer novel approaches to treatment or prevention.

While more research is needed, especially in clarifying cause versus effect, the gut–brain
axis is emerging as a key frontier in Parkinson’s disease. It suggests that future care may not
only target the brain but also focus on gut health as a pathway to protecting the mind.



Written By: Ellie Du

Sources:

Konings, B., Villatoro, L., Eynde, J.V. den, Barahona, G., Burns, R., McKnight, M., Hui, K.,
Yenokyan, G., Tack, J. and Pasricha, P.J. (2023). Gastrointestinal syndromes preceding a
diagnosis of Parkinson’s disease: testing Braak’s hypothesis using a nationwide database for
comparison with Alzheimer’s disease and cerebrovascular diseases. Gut. [online]
doi:https://doi.org/10.1136/gutjnl-2023-329685.

Yemula, N., Dietrich, C., Dostal, V. and Hornberger, M. (2021). Parkinson’s Disease and the
Gut: Symptoms, Nutrition, and Microbiota. Journal of Parkinson’s Disease, 11(4), pp.1491–
1505. doi:https://doi.org/10.3233/jpd-212707