Clinical Evidence For Probiotic Supplementation In Parkinson’s 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%.54 Constipation causes significant distress to many patients and can sometimes lead to serious complications such as intestinal pseudoobstruction, volvulus, and acute urinary retention.54 The problem is also often insufficiently responsive to currently available laxative treatments.55
In an openlabel 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 constipationassociated bloatedness, sense of incomplete emptying, and abdominal pain.56
Two subsequent doubleblind placebocontrolled randomized clinical trials have provided class I evidence for the use of probiotics as a treatment for constipation in PD.57, 58 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.57 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.
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 Parkinsons 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 Parkinsons 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.
Coffee & Tea For Parkinsons
Multiple studies have shown an association between caffeine intake and reduced PD risk. Different studies have noted this association across a range of dietary exposures including coffee, black tea, green tea and total caffeine intake.
The relationship between coffee or tea drinking and lower rates of PD is an association that is, the two tend to co-exist. We do not yet know if coffee and tea are the cause of the lower rates of PD. In addition, there are other potentially beneficial compounds in coffee and tea besides caffeine, some with anti-oxidant properties.
Researchers are exploring if there are contributions from these other substances that may contribute to the lower risk of PD. Recent research published by Dr. M. Maral Mouradian, interim director of one of APDAs Centers for Advanced Research at Rutgers-Robert Wood Johnson Medical School and member of APDAs Scientific Advisory Board, demonstrated how caffeine and Eicosanoyl-5-hydroxytryptamide may work together to prevent biochemical changes linked to development of PD. Although more research is necessary to test these compounds in humans and to determine how much of these substances are necessary to achieve the protective benefit, the research is pointing in the direction of coffee being beneficial.
Whether caffeine, coffee or tea is helpful to a person who already has PD is even less clear. That is, in addition to being associated with a lower risk of developing PD, could caffeine help PD symptoms?
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Small Intestinal Bacterial Overgrowth
Probiotics may also be beneficial for a condition known as small intestinal bacterial overgrowth in which there is excessive bacteria in the small intestine SIBO can cause symptoms such as abdominal pain, bloating, chronic diarrhea, and weight loss. Research studies have shown that this condition is more common in people with PD than in the general population, and has also been linked to worsened motor fluctuations in PD. Using probiotics to help treat SIBO may work by re-establishing a more normal bacterial environment. More research is necessary to better understand SIBO in patients with PD and to ascertain if probiotics are helpful for SIBO, specifically in the context of PD.
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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Ps128 And Parkinsons Patients
One initial study of PS128 with Parkinsons patients has given promising results, and randomized controlled trials are ongoing. 25 patients who had had Parkinsons for an average of 10 years were recruited for the pilot study. Each participant took 2 capsules of PS128 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 . 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*.
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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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.
Probiotics Benefit Parkinsons Disease In New Study
In a laboratory study using roundworms, researchers think they may have found a way of using probiotics to treat Parkinsons disease. The researchers suggest that administering a specific strand of probiotic bacteria could prevent the accumulation of the alpha-synuclein in the gut. The way that these probiotics benefit Parkinsons may lead to a more effective treatment of the disease if these findings are confirmed.
The study, which was conducted at the University of Edinburgh, involved genetically engineering a worm to develop with the human equivalent of the alpha-synuclein protein. Once they reached adulthood, the worms were fed a supplement that contained Bacillus subtilis PXN21, which is a strand of probiotic bacteria.
Upon examining the results, the researchers didnt find a difference in the levels of the alpha-synuclein protein itself, but they did observe that it didnt react with the gut in the same manner. Aggregates of the protein were cleared from the guts of the worms as the probiotic was introduced into their bodies. When compared to normal worms on a traditional diet, the genetically altered worms exhibited far lower levels of the aggregated protein while on the probiotic diet. The low level of protein aggregates remained consistent throughout the lives of the test worms.
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How Probiotics Might Help Pd Patients
For many years, Parkinson’s disease was thought to be an affliction of the brain, with the loss of neurons in the substantia nigra as the sole indication of deficiency. Many in the scientific community now strongly believe that PD is closely related to and in many cases caused by imbalances in the microbiome of the gut. The human brain communicates with the intestines and other digestive organs along the gut-brain axis. It is this line of communication that keeps a healthy balance of dopamine flowing throughout the brain and to the motor neurons that control all of our voluntary movements.
Currently, there is no cure for Parkinson’s disease, but there are science-backed options that can potentially help delay progression of the disease and alleviate some of its most uncomfortable aspects. For example, people who adhere to the Mediterranean diet, eating less refined sugar, salt, and saturated fat than the typical Western diet, may delay the onset of Parkinson’s disease by up to 17 years.
*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.
Current Gaps And Future Directions
Modification of the gut microbiome and/or metabolome using dietary,62 probiotics, and other approaches may provide new therapeutic, and possibly even preventative,63 options in PD. However, there currently remain many knowledge gaps surrounding the use of probiotics in PD. These offer a rich ground for further studies.
For a start, welldesigned and highresolution investigations on the gut microbiome and especially functional alterations in PD need to be conducted, and their findings need to be replicated and further dissected . In the general probiotic field, insights into probiotic mechanisms of action have mostly been gleaned from in vitro, cell culture, or animal studies,38 and future research should also incorporate studies investigating their actions in humans .39
The clinical effects of probiotic supplementation on important PD features, including parkinsonian motor disability, motor response complications , and other common nonmotor symptoms such as cognitive impairment, depression, anxiety, and psychosis, are important areas for further research. Longerterm studies examining probiotic efficacy and safety are needed, although these may be quite challenging to perform, particularly in PD . Another major barrier in PD clinical research has been the lack of reliable biomarkers for measuring disease severity and, therefore, the need to rely on clinical rating scales with their inherent limitations.60, 64, 65, 66, 67
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Psychobiotics: Influencing The Brain From The Gut
But the gut isnt 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 ones 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 well 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.
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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Downsides Of Probiotics For Parkinsons
Although probiotics are generally considered safe, there are some potential concerns with probiotic supplementation in people with Parkinsons disease .
First, some Enterococcus species found in some probiotic supplements may inactivate levodopa, a dopamine-replacement medication used in the treatment of PD. However, this needs more research and clarification in PD patients .
Further, probiotic supplementation may exacerbate SIBO , common in people with Parkinsons disease .
Its also unknown which probiotic strains are most effective in treating PD symptoms and if theyre more effective in combination or taken as single strains.
An individualized assessment of the microbiome may be warranted to determine the best course of action (
Variance Stabilizing Transformation And Deseq2 Analyses
Since the DESeq2 approach does not account for zero-inflated data, the correction factors were calculated using the GMPR method that is based on geometric means of pairwise ratios. Euclidean, BC, and JSD distances were used as beta-diversity estimators after normalizing the data via VST through the DESeq2 package. Statistical differences between control and PD groups were tested using the adonis2 function as specified above. DAs were calculated using default DESeq2 parameters that include a negative binomial GLM fitting and a Wald test. Multiple testings were accounted for using BH P value correction.
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Causes & Symptoms Of Parkinsons 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