Researchers Harness Probiotic Bacteria To Deliver Parkinsons Disease Treatment
Animal studies show live biotherapeutic produced by gut-healthy probiotic bacteria is safe, reduces treatment complications.
Researchers have engineered probiotic bacteria that can synthesize the dopamine precursor L-DOPA, a powerful mainstay treatment for Parkinsons disease. Preclinical tests show that the new treatment approach is not only safe and well-tolerated but also eliminates side effects that eventually develop when L-DOPA is taken orally.
We are harnessing the metabolic capability of beneficial microbes that live in the gut to synthesize a molecule that is the gold standard therapeutic strategy for Parkinsons disease, said Anumantha Kanthasamy, PhD, professor and Johnny Isakson Chair, Georgia Research Alliance Eminent Scholar at the University of Georgia in Athens, Ga. This next-generation microbial bioengineering technology is designed so that Parkinsons patients could make their own L-DOPA with microbes in their gut.
Piyush Padhi, a doctoral student in Kanthasamys lab, presented the new research at the American Society for Pharmacology and Experimental Therapeutics annual meeting during the Experimental Biology 2022 meeting, which was held on April 2-5, 2022, in Philadelphia.
To address this challenge, Kanthasamys research team used newly developed synthetic biology and genetic engineering techniques to generate a safe and tolerable probiotic bacterium that can synthesize L-DOPA from tyrosine produced by the body.
Meeting: Experimental Biology 2022
What Else Can A Probiotic/prebiotic Supplement Do For You
Supplementing with a probiotic formula, or otherwise ensuring that you are getting adequate levels of probiotics in your everyday diet, can do wonders for your overall health. A healthy balance of probiotics in the gut has been linked to everything from stress resilience to liver health. Recent studies have found that in order to receive the full benefit of probiotics, its essential to find a high-quality supplement that provides both probiotics and prebiotics.
How Is The Microbiome Different In People With Pd
Based on numerous studies comparing the microbiome from the gut of people with PD with the microbiome from the gut of people without PD, there appear to be some differences. The studies are not consistent in their findings, but there are similarities across studies. These include an increase in certain families of bacteria such as Lactobacillaceae and Verrucomicrobiaceae, and a decrease in the family Prevotellaceae.
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Several Pathways Working Together
To find out how B. subtilis is able to prevent and clear alpha-synuclein aggregates, the team used RNA sequencing analysis to compare the gene expression of animals receiving a standard diet with that of those receiving the probiotic.
This analysis revealed changes in sphingolipid metabolism. Sphingolipids are a type of fat molecule, and they are important components of the structure of our cell membranes.
Previous studies suggest that an imbalance of lipids, including ceramides and sphingolipid intermediates, may contribute to the pathology of , the authors comment in the paper.
Yet, changes in sphingolipid metabolism were not the only pathways that the researchers identified.
They also saw that B. subtilis was able to protect older animals from alpha-synuclein aggregation through both the formation of complex structures called biofilms and the production of nitric oxide. In addition, the team saw changes in the dietary restriction and the insulin-like signaling pathways.
Importantly, when the team switched animals that had first received a standard diet over to a B. subtilis diet, their motor skills improved.
The results provide an opportunity to investigate how changing the bacteria that make up our gut microbiome affects Parkinsons. The next steps are to confirm these results in mice, followed by fast-tracked clinical trials since the probiotic we tested is already commercially available.
Probiotics May Aid In Relieving Parkinson Diseaserelated Anxiety
Research led by Vancouver Coastal Health Research Institute scientist Dr Silke Appel-Cresswell is the first to examine whether a multistrain probiotic could help relieve anxiety symptoms in people with Parkinson disease. Parkinson disease often causes muscle rigidity linked to reduced dopamine levels, along with tremors or slowed movements. Dopamine replacement therapy can help relieve symptoms of anxiety and stiffness among some patients, but existing treatments take a while to kick in, and often wear off within a few hours.
For her randomized, triple-blind and placebo-controlled clinical trial, Treating Anxiety in Parkinsons Disease with a Multi-Strain Probiotic , Appel-Cresswell is recruiting adults with Parkinson disease ages 40 to 80 to investigate the effectiveness of the Ecologic BARRIER849 probiotic as an anxiety reduction treatment. The over-the-counter probioticnot currently available in Canadian storescontains a mixture of live bacterial cultures targeted at promoting a healthy gut flora, which the research team believes may set off a chain reaction that stops the anxiety cycle.
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Prediction Of Gut Metabolic Modules And Bioactive Fmetabolites
A module-based analytical framework described by Valles-Colomer and MetaCyc metabolic database were used to predict SGBs encoding related GMMs. For each SGB, the predicted open reading frames were compared with the Kyoto Encyclopedia of Genes and Genomes Orthologies database to annotate the key gut-brain metabolic modules. The SGBs encoding related modules were identified by Omixer-RPM using the parameter -c 0.66.
Gut metabolites were predicted based on high-quality sequences. One million reads per sample were subsampled using seqtk , and the subsamples reads were compared by the blastx function of DIAMON -query-cover 90-id 50. The best hit of each gene was selected for the calculation of the gene abundance profile of each sample. Then the MelonnPan-predict workflow was used to convert gene abundances into a predicted metabolomic table.
Causes & Symptoms Of Parkinson’s Disease: An Overview
On the neurological level, PD is thought to be the result of a buildup of toxic proteins that kill off neurons in a part of the brain called the substantia nigra. Certain neurons in this part of the brain are responsible for making dopamine. Dopamine is a neurotransmitter and hormone that is vital for many important functions, including movement, memory, and motivation.
Scientists believe that lower dopamine levels cause the motor symptoms of PD, as well as many psychological disorders. Unfortunately, clinical studies have not been able to pinpoint the reason why the toxic proteins begin to build up in the substantia nigra in the first place. It is theorized that this occurs due to a combination of genetic and environmental factors.
There are two types of PD. In one type, the damage is first observed in the brain as a loss of neurons. In the other type, symptoms originally present as inflammation in the intestinal lining.
The gut-brain axis is also involved in the pathogenesis and symptoms of Parkinsons disease. The loss of dopamine-producing neurons in the brain results in the reduction of dopamine which, in turn, leads to an onset of neurological symptoms. In some cases, inflammation of the intestinal lining plays a role in the progression of PD, and gastrointestinal symptoms may be present for years prior to neurological symptoms.
- A tremor in the hands, limbs, jaw, or head
- Difficulty with balance and coordination
- Muscle stiffness
- A slow, shuffling gait
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Parkinsons And Gut Health
The findings of this research project, which was co-funded by Parkinsons UK, build on previous research linking brain function to gut bacteria.
Dr Beckie Port, Research Manager at Parkinsons UK, said: Changes in the microorganisms in the gut are believed to play a role in the initiation of Parkinsons in some cases and are linked to certain symptoms. That’s why there is ongoing research into gut health and probiotics.
Studies that identify bacteria that are beneficial in Parkinson’s have the potential to not only improve symptoms but could even protect people from developing the condition in the first place.
The Pros Of Probiotics
One strategy to try and reintroduce good bacteria is to use a treatment called faecal transplantation. This involves collecting bacteria that live in the gut of a healthy donor from a stool sample, and preparing and transplanting them via a tube directly into the gut of the recipient. But while this may work for some conditions where the gut microbiota is abnormal, the process is difficult and still needs regulatory approval and safety checks before it could be made available more widely. So, researchers have been investigating other ways to get good bacteria back into the gut.
A faecal transplant may provide a more direct route for live bacteria to reach the gut but what about oral probiotics? Unfortunately, the bacteria in many commercial probiotics are unlikely to reach the lower gut, where they are needed, as most types of bacteria are wiped out on route by the acidic environment in the stomach. However, with the right combination of good bacteria and delivery mechanism, this may not be inevitable.
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Researchers At The International Parkinsons Centre Of Excellence At Kings College Hospital Nhs Foundation Trust Led By Prof K R Chaudhuri Are About To Embark On A Study That May Potentially Change The Way We Treat Parkinsons
Today, Parkinsons is treated using medications that mask the problems happening in the brain. These medications which aim to replace or mimic the effect of the chemical messenger dopamine can be very effective at addressing some of the motor symptoms of Parkinsons, particularly in the early stages. But they are often less effective for the non-motor symptoms like pain, anxiety, and constipation.
Now, a world-first UK-led clinical trial is due to begin to test if a probiotic drink could help improve both the motor and non-motor symptoms of Parkinsons by improving gut health.
Research Shows Bacteria Strain Could Guard Against Parkinsons
Bacillus subtilis PXN® 21® found within leading bacteria brand Bio-Kult that boosts digestive health can slow and even reverse build-up of a protein associated with Parkinsons, new research in worms suggests.
Building on previous research linking brain function to gut bacteria, this study in a Parkinsons model of roundworms, identified that a strain from our Bio-Kult product line Bacillus subtilis PXN® 21® helped prevent the formation of toxic clumps that starve the brain of dopamine, a key chemical that coordinates movement. These new findings could pave the way for future studies that gauge how supplements such as live bacteria impact the condition.
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Central Nervous System Lymphatics
Louveau et al56 discovered a network of lymphatic vessels lining dural sinuses carrying both fluid and immune cells from cerebrospinal fluid. This observation opens the door to the possibility that cytokines from the GI tract may interact more with the CNS than previously understood. Any microbial dysbiosis that potentially triggers an inflammatory cascade in the CNS can potentially cause dysfunction of the immune system, leading to the development of neurodegenerative diseases like PD.
Scientists Create A Probiotic For Treatment Of Parkinsons Disease
Probiotics are good for the gut, and new research suggests they could also improve symptoms of Parkinsons disease. Scientists have engineered a probiotic bacterium to create L-DOPA which later gets converted into dopamine. Animal studies show the unique treatment is not only safe, but also takes away any side effects of taking L-DOPA orally.
People with Parkinsons disease have low dopamine levels. A common treatment is to replace the dopamine using levodopa L-DOPA tablets that need to be taken orally 3 to 4 times a day. The treatment is effective in reducing Parkinsons symptoms but problems with motor control occur 5 years after taking the medication. This likely occurs because the delivery of L-DOPA to the brain is not constant.
We are harnessing the metabolic capability of beneficial microbes that live in the gut to synthesize a molecule that is the gold standard therapeutic strategy for Parkinsons disease, says Anumantha Kanthasamy, PhD, professor and Johnny Isakson Chair of the Georgia Research Alliance Eminent Scholar at the University of Georgia. This next-generation microbial bioengineering technology is designed so that Parkinsons patients could make their own L-DOPA with microbes in their gut.
When testing the treatment on rodents and dogs, the team found consistent L-DOPA levels in the blood and brain. In a mouse model of Parkinsons disease, the probiotic improved motor, cognitive, and mood symptoms.
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Clinical Evidence For Probiotic Supplementation In Parkinsons Disease
Several studies have demonstrated the benefits of probiotic supplementation in PD patients, particularly as a treatment for constipation. Constipation is a very common symptom in PD, with a reported prevalence of up to 70%. Constipation causes significant distress to many patients and can sometimes lead to serious complications such as intestinal pseudo-obstruction, volvulus, and acute urinary retention. The problem is also often insufficiently responsive to currently available laxative treatments.
In an open-label study of 40 PD patients, supplementation of fermented milk containing Lactobacillus casei Shirota , together with diet therapy, for 6weeks was associated with a significant increase in the number of days of bowel opening with normal stool consistency and improvement in constipation-associated bloatedness, sense of incomplete emptying, and abdominal pain.
Two subsequent double-blind placebo-controlled randomized clinical trials have provided class I evidence for the use of probiotics as a treatment for constipation in PD., In the first RCT, 120 PD patients were randomized to receive either fermented milk containing multiple probiotic strains , combined with prebiotic fiber , or a placebo for 4weeks. There was a significant increase in the number of complete bowel movements per week, as measured by stool diary, as well as improvements in bowel frequency, stool consistency, and frequency of laxative usage, in the treatment group.
Could A Probiotic Prevent Or Reverse Parkinson’s
Because the misfolded protein that appears to kill dopamine-producing neurons in the brain in Parkinsons disease may originate in the gut in some people, potential prevention strategies could target both gut and brain. Probiotics might be able to help in both ways, but further human studies are required.
In the gut, Lactobacillus acidophilus and L. plantarum have been shown to prevent and repair inflammation in the intestines, which is the leading cause of altered communication in the gut-brain axis. Probiotics like these are already commonly used in the treatment of constipation, and constipation as a symptom of PD is no exception.
Beyond alleviating a distressing non-motor symptom for PD patients, gut health probiotics might also have a potentially preventative role to play. Some people experience GI tract symptoms for up to a decade prior to experiencing the neurological symptoms of PD. If probiotics could alleviate the chronic GI symptoms that precede PD for so many patients, could the onset of neurological symptoms be slowed or prevented? The answer to this question is as yet unknown, but future long-term human studies may shed more light.
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Intervention Mediated By The Microbiota
Diet
Olive oil, the main source of fat in the Mediterranean diet, mainly contains monounsaturated fatty acids, which have antioxidant activity and inhibit synuclein aggregation. Phenolic compounds in olive oil have anti-inflammatory, antioxidant, neuroprotective and immunomodulatory activities. In addition, the Mediterranean diet contains several antioxidants, including vitamin E, vitamin C, folic acid and polyphenols. Yang et al. prospectively evaluated the relationship between the dietary antioxidants vitamins C and E and carotene and the risk of Parkinson’s disease and found that dietary vitamin E and carotene intake can reduce the risk of developing the disease. These antioxidants can neutralize the role of oxygen free radicals to reduce oxidative damage. A recent study in Caenorhabditis elegans Parkinson’s disease models showed that the main olive oil polyphenols, hydroxytyrosol and oleuropein aglycone, can reduce the accumulation of α-synuclein in muscle cells and prevent the neurodegeneration of dopaminergic neurons containing α-synuclein.
Figure 4.
Probiotics
Prebiotics and Micronutrients
Faecal Microbiota Transplantation
The Gut And Parkinsons
There appears to be a greater connection between gut and brain in the disease process of PD not formerly recognized. No wonder ancient Japanese civilizations believed that the center of wisdom was the gut. We allude to this when we use the term “gut feelings.” According to recent studies, people with Parkinsons not only have different flora in their gut compared to those without PD, but also have a specific bacteria known as Enterobacteriaceae, which has a direct correlation in symptom presentation. Those who have a greater number of this pathogen in their system appear to have an increased difficulty with gait and balance.
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Link Between Parkinson’s And The Gut Microbiome
Studies have shown that people with Parkinson’s disease have an abnormal presence of a protein called alpha-synuclein, which the vagus nerve carries from the brain to the gut. This may explain the higher presence of protein aggregates in the gut microbiomes of people with Parkinson’s disease.
Since researchers know that alpha-synuclein is linked to the disease, a higher presence of the protein in the gut may help diagnose the disease before symptoms manifest. If the research can be confirmed, this may lead to more effective treatments in both preventing the illness and in controlling the symptoms for those who already have the disease.
Probiotics May Benefit Patients With Parkinson Disease
Evidence suggests probiotics may decrease pro-inflammatory cytokines, oxidative stress, and potentially pathogenic bacterial overgrowth in patients with Parkinson disease.
In vitro evidence suggests probiotics may decrease pro-inflammatory cytokines, oxidative stress, and potentially pathogenic bacterial overgrowth in patients with Parkinson disease , according to a study in Frontiers in Immunology. The study was conducted to investigate whether the use of probiotics could benefit patients with PD.
Despite the great interest that recently arose around the gut-brain axis in health and disease, our study is the first to specifically address the effect of probiotics on mediators of inflammation and oxidative damage in peripheral blood mononuclear cells of PD patients, researchers wrote.
A total of 80 participants were enrolled for the study. Half of the participants were patients with PD while the other half were age-matched healthy donors recruited for the studys control group. The PD group included 15 women and 25 men with a mean age of 70 years while the control group included 18 women and 22 men with a mean age of 68 years. Patients were followed-up regularly at the Movement Disorder Center of Maggiore Hospital in Novara, Italy.
Overall, our preliminary findings suggest a potential role for probiotic strains in modulating inflammation and oxidative stress and protecting the epithelium from gut permeability. researchers concluded.
Reference
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