How does the neurologically active PS128 probiotic work?

The organ with the second largest number of nerve cells besides your brain is your gut. Often called the “2nd brain”, the enteric nervous system connects to the central nervous system via the vagus nerve and other pathways. This so-called gut-brain axis (GBA) enables two-way communication between the brain and the intestines. It also includes your gut contents: the trillions of bacteria, yeasts and viruses of the gut microbiota.

The GBA is of special interest to people with Parkinson’s disease (PD) and their loved ones. It plays a role both in the development of PD. Also, certain neurologically active probiotics appear to utilize the GBA to modulate levels of neurotransmitters like dopamine in the brain. In this article I’ll discuss how one of those unique probiotics may do that.

The Gut-Brain Axis and the Origin of PD

PD may start in the gut, at least in some people. Accumulation of aggregates of ⍺-synuclein in the dopamine-producing neurons of the substantia nigra is thought to cause them to die. As dopamine levels drop, the familiar motor symptoms of PD begin to appear. But as many as 10 years before this, aggregates of ⍺-synuclein can already be spotted in intestinal nerve cells.

Gut enteroendocrine cells, it turns out, are able to synthesize this protein. It’s not known why ⍺-synuclein forms aggregates in the gut, but gut dysbiosis, or the imbalance of good and bad microbes within the gut microbiome, may play a role. The ⍺-synuclein aggregates can then travel from gut to brain via the vagus nerve. People who have undergone partial or complete removal of the vagus nerve have a decreased risk of developing PD.

Psychobiotics: Influencing the brain from the gut

But the gut isn’t just the bad guy in this story. It also has the potential to slow down development of PD at both ends of the gut-brain axis through the use of specific probiotics.

Since poor gut health can lead to the development of PD, proactively addressing one’s gut health may help to prevent or slow onset of PD. Probiotics are one way to improve gut health. Certain probiotics called psychobiotics can also support neurological and mental health. Without leaving the gut, these unique probiotics somehow affect levels of one or more neurotransmitters in the brain.

Today we’ll focus on one particular psychobiotic, L. plantarum PS128. A study of PD patients shows that it may support movement and improve quality of life for PD patients*. Studies with animals give us hints of how PS128 can affect the brain from its home in the gut.

PS128 and Parkinson’s patients

One initial study of PS128 with Parkinson’s patients has given promising results, and randomized controlled trials are ongoing. 25 patients who had had Parkinson’s for an average of 10 years were recruited for the pilot study. Each participant took 2 capsules of PS128 (a total of 60 billion CFUs) per day for 12 weeks in addition to their usual dose of levodopa and any other medications.

At the end of the study, there was a statistically significant improvement in akinesia (difficulty moving). This was measured by the ability of participants to perform finger, hand, and leg movements with agility. Improvements in akinesia were seen both in the ON state when a levodopa dose was maximally effective, and in the OFF state in the low point between doses.

Other movements such as tremor and postural stability were not improved in the study, but rigidity trended toward improvement. Participants also reported longer ON time and less OFF time by about 45 minutes per day. Overall, 68% of participants noted they felt PS128 helped them, with 20% saying they felt much or very much improved*.

PS128 mechanisms of action – what animal studies say

But how does PS128 work? How could akinesia and activities of daily living be improved by a probiotic strain that never leaves the gut? Studies of PS128 in mice and rats offer us some clues.

Increased dopamine activity

PD patients have approximately 80% fewer dopamine-producing neurons in their substantia nigra (SN) compared with adults without PD.  Motor symptoms of PD such as akinesia derive from a lack of dopamine activity in this area of the brain.

Three animal studies show that mice taking PS128 have higher amounts of dopamine in their brains compared with those that do not take PS128. In these studies, the mice taking PS128 also moved more than those that did not take the probiotic.

The mechanisms by which PS128 influences dopamine levels appear to be complex. In one study, researchers saw that the dopamine transporter is produced in higher numbers in rodents taking PS128, potentially improving the ability of nerve cells to store dopamine and use it as needed. In another, the turnover rate of dopamine was significantly reduced in the brains of PS128-fed rats, leading to a longer half-life of this key neurotransmitter. Taken together, these studies suggest that PS128 may not necessarily cause the brain to “make” more dopamine, but it may instead help the brain do more with the dopamine that is already available.

Anti-inflammatory and antioxidant activity

PS128 appears to help with oxidative stress and inflammation in both humans and rodents. This property has a neuroprotective effect in animals.  In mice treated with oxidizing substances within the brain, PD-like motor symptoms developed. These symptoms were significantly decreased if the mice were also given PS128, and more intact dopaminergic neurons were seen in the SN in these animals.

Intriguingly, decreased levels of a pro-inflammatory protein called MPO are measured in the bloodstream of PD patients taking PS128. These results suggest that PS128 may have anti-inflammatory properties in people as well. It is not yet known if this property of PS128 can protect dopaminergic neurons from dying in humans.

PS128 and dopamine

We don’t yet know exactly how PS128 combats akinesia and improves quality of life for the people that it helps*. However, studies in animals suggest it may play a role in dopamine production and metabolism, partially compensating for lost neurons. PS128 may also reduce inflammation in the brain that kills dopamine producing neurons, thereby slowing disease progression*. As we learn more about the gut-brain axis, perhaps we will understand better how tiny microbes can do all this from their home inside the gut.

Bened Life is on a mission to help people with neurological and mental health conditions with gut-brain probiotics. Neuralli is a daily medical probiotic that provides the clinical dose of L. plantarum PS128. Visit benedlife.com to learn more about Neuralli.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.