Prebiotics balance gut bacteria and show results in Parkinson’s blood

A specialized prebiotic supplement can restore healthy gut bacteria in people with Parkinson’s disease, and researchers have discovered a way to track this progress through a simple blood test. By measuring tiny particles in the blood that carry signals between the gut and the brain, scientists can now observe how the body responds to the treatment in real time. This discovery offers a potential new method for doctors to monitor Parkinson’s biology and evaluate new therapies without invasive procedures.

Extracellular vesicles are small particles released by cells that carry proteins, fats, and genetic material to communicate with other cells. They can cross from the blood into the brain and carry signals from both the body and gut bacteria, giving a real-time, whole-body view of how the gut and brain interact.

“Our findings provide a novel and compelling foundation for future research, supporting the feasibility of using [extracellular vesicles] as a minimally invasive platform for tracking disease biology,” researchers wrote in “Prebiotic intervention changes host and microbe proteomes in plasma extracellular vesicles of Parkinson’s disease,” published in Scientific Reports.

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March 14, 2023 News by Patricia Inácio, PhD

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The gut-brain connection in Parkinson’s

Gut dysbiosis — an imbalance in gut bacteria where harmful bacteria overgrow beneficial ones — has been linked to Parkinson’s. Growing evidence suggests that restoring a healthy gut may help regulate the gut-brain axis, a two-way communication system between the gut and the brain, easing symptoms of Parkinson’s.

In a previous proof-of-concept clinical study (NCT04512599), a fiber-rich prebiotic bar restored balance to the gut environment and eased both motor and nonmotor symptoms in a small number of patients. In this study, the same researchers sought to go further and determine whether extracellular vesicles can serve as biomarkers of response to prebiotics.

“Prior studies provide compelling data for [extracellular vesicles] as a promising and accessible source for diagnostic biomarkers for neurodegenerative diseases like [Parkinson’s],” the researchers wrote. Easily collected from blood samples, extracellular vesicles “provide a unique systemic snapshot by carrying both host and bacterial proteins across the blood–brain barrier,” they added.

The study included blood samples from 20 adults with Parkinson’s collected before and after 10 days of prebiotic supplementation. As controls, it included blood samples of 10 healthy adults. Mass spectrometry, a technique that identifies and quantifies proteins based on their molecular weight, was used to detect both human and bacterial proteins in extracellular vesicles.

The researchers first confirmed that the extracellular vesicles were properly collected and were consistent in size and shape using imaging and particle-tracking techniques. Interestingly, patients had fewer extracellular vesicles in their blood compared with healthy adults, although the size and total protein content were similar. More than 630 different proteins were identified.

The set of proteins, known as the proteome, present in extracellular vesicles from patients differed from that of healthy adults. However, after 10 days of prebiotics, the proteome shifted closer to that of healthy adults, regardless of whether patients were untreated or already receiving treatment for Parkinson’s.

To understand which proteins were most important, the researchers looked for those that changed significantly between groups. Many of these proteins are involved in the immune system. The immune system has two main types of response: innate, the body’s first line of defense, and adaptive, which is more specialized. Patients had more proteins involved in the adaptive response.

Some proteins were linked to inflammation and oxidative stress, which refers to damage caused by unstable molecules called free radicals. Both play roles in neurodegenerative diseases such as Parkinson’s. Treated patients with moderate disease had significantly higher levels of APOD, a protein that responds to inflammation and oxidative stress.

Other proteins, such as ANK1, SPTA1, and EPB41, which can help maintain the structure and mechanical stability of the gut lining, were also more abundant in patients, suggesting ongoing inflammation or a weakened barrier that the body attempts to repair to prevent bacteria from entering the bloodstream. Prebiotics shifted these protein patterns toward normal levels.

A new tool for Parkinson’s diagnosis

When the researchers examined bacterial proteins in extracellular vesicles, they found them more abundant in blood samples from patients, supporting the idea that the gut lining may be compromised. After prebiotic treatment, bacterial protein levels decreased relative to those of the human host.

To confirm this, the researchers compared blood with stool samples from the same patients. About half of the most variable bacterial proteins found in extracellular vesicles matched those present in stool samples, indicating that extracellular vesicles in blood can reflect the bacteria living in the gut. Prebiotics increased beneficial bacteria, while reducing harmful ones.

Finally, the researchers built a statistical model using 16 proteins, both human and bacterial. This model could accurately distinguish patients from healthy adults and estimate disease severity. This suggests that extracellular vesicles provide a window into gut bacteria and that their proteome could become a useful tool for diagnosing and tracking Parkinson’s.

While the number of patients was small, “this study is, to our knowledge, the first to integrate host and microbial [extracellular vesicle] proteomics to assess [Parkinson’s] status and the effects of a prebiotic intervention,” the researchers wrote. “Future work should aim to validate these findings.”