New Link Between Parkinson's Disease and the Gut

Scientists have long suggested there is a link between Parkinson's disease and the gut. A new study explains why this neurodegenerative disorder may start in the gut years before the first neurological symptoms appear.

The theory that Parkinson's disease may start in the gut was first introduced 20 years ago. Since then, evidence of the link between the two has been emerging: according to a large 2021 study, Parkinson's patients have disbalance in the gut microbiome, such as excess pathogens and species associated with inflammation. Another recent research identified specific gut bacteria that may cause Parkinson's disease.

Researchers at the Columbia University Irving Medical Center (CUIMC) have previously shown that an autoimmune response may play a role in developing the disease.

In Parkinson's patients, a protein called alpha-synuclein becomes misfolded, accumulates inside neurons, and slowly poisons the cells. Small portions of the misfolded alpha-synuclein also can appear on the outside of neurons, making them vulnerable to attack from the immune system, which could impose more acute damage to the neurons than the internal deposits of the protein.

While the blood of Parkinson's patients often contains immune cells that are primed to attack the neurons, it remains unclear where or when they are doing so.

In the new study that appeared in the journal Neuron, CUIMC researchers, in collaboration with immunologists at the La Jolla Institute of Immunology, examined why an immune reaction to alpha-synuclein may lead to disease development.

First, they created a mouse capable of displaying pieces of misfolded alpha-synuclein on cell surfaces, as normal mice don't have this ability. Then, they injected the mice with alpha-synuclein and monitored changes in the brain and the gut.

Although no signs resembling Parkinson's disease in the brain were observed, an immune attack on neurons in the gut caused constipation and other gastrointestinal issues. Most Parkinson's patients experience similar symptoms years before they are diagnosed with the disease.

This shows that an autoimmune reaction can lead to what appears to be the early stages of Parkinson's and is strong support that Parkinson's is, in part, an autoimmune disease.

- David Sulzer, Ph.D. at CUIMC and study author

The researchers hope that the findings may pave the way for early detection of Parkinson's disease. This could potentially help to interrupt an immune response in the gut to prevent a later attack on the brain's neurons and, as a result, Parkinson's disease.

However, scientists still don't know how significant the immune system's role is in Parkinson's brain. The study authors hypothesize that the brains of the mice did not develop any signs of Parkinson's because the animals are young and age has not yet weakened the blood-brain barrier.

Parkinson's is the second most common neurodegenerative disease after Alzheimer's. Nearly one million people in the United States are living with Parkinson's disease, and the number is expected to rise to 1.2 million by 2030.

The causes of Parkinson's disease are not well understood, but scientists think it may be a combination of age, genetic and environmental factors.

According to the Parkinson's Foundation, early signs of the disease include:

• Tremor or a slight shaking in the finger, thumb, hand, or chin.
• Changes in handwriting, such as smaller letter sizes and the words being crowded together.
• Loss of smell that is not caused by a cold, flu or a stuffy nose.
• Trouble sleeping, including sudden movements during sleep.
• Stiffness in the body, arms, or legs, as well as pain in the shoulder or hips.
• Constipation, even if you drink enough water, follow a high-fiber diet, and do not take medication that causes trouble with bowel movements.
• Changes in voice, as it becomes very soft or breathy and/or hoarse.
• Masked face which is a serious, depressed, or mad facial expression even when a person is not in a bad mood.
• Dizziness or fainting, for example, when standing up from a chair.
• Stooping or hunching over.

The new study offers a deeper understanding of the link between Parkinson's disease and the gut; however, human studies are necessary before developing new therapies based on the findings.