Probiotics For Parkinson Patients
In light of this, the chief physician Dr Martin Heine, head of the neurology department at the Feldbach/Fürstenfeld state hospital, conducted a pilot study: Over a time period of 8 weeks, doctors studied the effects of special multi-species probiotics on the digestion and motor function of Parkinson patients. Results show that the stool frequency clearly increased through the use of the probiotics, and especially the form and consistency improved vastly: Before starting the probiotic therapy, the stool consistency was a clear indication of constipation . After the 8-week probiotics intake, patients had optimal faeces. Notably positive was the fact that the Parkinson patients didnt suffer from unwanted reactions such as diarrhoea or bloating, as opposed to standard laxatives.
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Dietary Probiotics Show Potential To Reverse Parkinson’s Symptoms
January 14, 2020 — Roundworms that were fed a commercially available dietary probiotic showed less buildup of proteins that form during the progression of Parkinson’s disease in a new study, published in Cell Reports on January 14. The finding provides further evidence of a link between the gut microbiome and brain function.
Parkinson’s disease is one of the most prevalent neurodegenerative diseases and is characterized by progressive loss of dopaminergic neurons in the substantia nigra region of the brain. The condition stems from the accumulation of proteins called alpha-synuclein that can aggregate in the brains of individuals. -syn acquires neurotoxic properties when protein monomers progressively combine to form insoluble amyloid fibrils.
“Parkinson’s is the fastest-growing neurological condition in the world,” said Beckie Port, PhD, a research manager at Parkinson’s UK, which cofunded the research. “Currently, there is no treatment that can slow, reverse, or protect someone from its progression but by funding projects like this we’re bringing forward the day when there will be.”
Recent research provides evidence that signals peripheral to the central nervous system, particularly from the gastrointestinal tract and gut microbiota, are involved in the progression of Parkinson’s disease. For example, -syn pathology begins in peripheral tissues such as in the intestines and gradually spreads to multiple brain regions.
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.
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Experimental Model And Subject Details
Nematode and bacterial strains
All bacterial and nematode strains used and generated in this study can be found in the Key Resources Table.
C. elegans NL5901 pkIs2386 was kindly provided by Ellen Nollen. C. elegans N2 and all the mutant strains used for the generation of the different pkIs2386 derived strains were obtained from the Caenorhabditis Genetics Center and the Million Mutant collection .
Strains obtained from the CGC are: CB1370 daf-2, CF1038 daf-16, PS3551 hsf-1, DA465 eat-2, VC747 lagr-1, RB1579 sptl-3, RB1487 asm-3.
The molecular identity of these alleles is as follows: daf-2 is a missense reference allele, daf-16 and lagr-1 are deletion, loss of function alleles. eat-2 and hsf1 are nonsense alleles. asm-3 is a complex substitution allele removing most of the last 7 exons, sptl-3 is a deletion removing exons 5 to 9.
The following strains were generated in this study: MDH586 daf-2 III pkIs2386, MDH585 daf-16 I pkIs2386, MDH587 hsf-1 I pkIs2386, MDH657 daf-2 III daf-16 I pkIs2386, MDH614 daf-2 III pkIs2386, MDH611 eat-2 II pkIs2386, MDH711 lagr-1 I, pkIs2386, MDH725 sptl-3 II pkIs2386, MDH724 asm-3 IV pkIs2386.
The Intestines As The Centre Of Diseases
Often enough, many years before the motoric symptoms, unspecific symptoms such as back and shoulder pain, altered handwriting, disturbances in circulatory regulation, smell impairment and constipation arise. The first signs of Parkinsons disease can be found in the gut if you look for it directly: Patients who were diagnosed with Parkinsons at an early stage showed a specific protein in the nervous system of the intestinal wall. This so-called Alpha-synuclein is responsible for killing off dopamine-producing nerve cells. Furthermore, Parkinson patients also have an altered gut-flora composition. These insights clearly show that the gut-brain, the so-called enteric nervous system, and the gut-brain-axis play a central role in the development of Parkinsons.
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Could A Common Probiotic Bacteria Prevent Parkinson’s Disease
RESEARCHERS were shocked after a probiotic already available in shops showed “remarkable” abilities to prevent and even destroy toxic protein clumps linked to the onset of Parkinson’s disease.
Scientists at the universities of Edinburgh and Dundee want to launch human clinical trials with the bacteria as soon as possible amid hopes that the discovery could pave the way to a dietary-based intervention to halt the progression of the disease.
So far the results have only been demonstrated in roundworms, but the findings are the latest evidence of a relationship between the gut and Parkinson’s disease.
It is already known that the brains of people with Parkinsons disease become riddled with a build-up of mis-folded proteins called alpha-synuclein, which form toxic clumps.
These clumps are associated with the death of neurons responsible for producing the pleasure hormone, dopamine.
The loss of these cells causes the motor symptoms associated with Parkinsons, including freezing, tremors and slowness of movement.
However, these clumps have also been found in the gut, leading to the theory that they may spread from from the digestive system to the brain.
When roundworms engineered to mimic Parkinson’s were fed bacteria from various over-the-counter probiotics, they found that Bacillus subtilis – known to boost digestive health – protected against the build-up of this protein and also cleared some existing clumps.
Potential Roles And Mechanistic Effects Of Probiotics
Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer health benefits to the host. The therapeutic and prophylactic effects of probiotic administration are thought to be mediated through a wide assortment of mechanisms, which have been well described elsewhere,, , and are briefly summarized here.
The host gut microbiota can be impacted by probiotic supplementation through competition , antagonism, and crossfeeding., The formation of biofilms by probiotic bacteria promotes colonization and longer permanence in the mucosa of the host and avoids the attachment of pathogenic bacteria. Many probiotic strains are antagonistic toward other microorganisms due to the production of organic acids , which lower luminal pH, and also bacteriocins, which inhibit pathogens in the human gut and urinary tract. Interestingly, supplementation with Lactobacillus probiotics during Helicobacter pylori eradication therapy has been found to improve eradication efficacy, presumably due to their antagonistic activity against H. pylori. Crossfeeding between probiotic bacteria and host microbiota can promote the production of SCFAs such as butyrate in the gut, with benefits as described above.
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Our Gut Microbiome Is Our Internal Ecosystem Which Consists Of Trillions Of Microorganisms Including Thousands Of Different Types Of Bacteria The Diversity Of Our Microbiome Is As Unique As Our Fingerprint And Its Known That Our Gut Microbes Offer Many Benefits To Our Health Certain Bacterial Strains Are More Researched Than Others And More Research Is Constantly Emerging In This Exciting Field Here At Link Nutrition Were Mad About Gut Health
Probiotics, like our Synbiotic 7, are often used to improve the diversity of the bacteria within the gut, with the most popular being Lactobacillus and Bifidobacterium strains. However, a specific strain called Bacillus subtilis is one example of a bacterial strain which has been shown to have beneficial probiotic characteristics, and is the most abundant strain in our Synbiotic 7, with 10 billion colony forming units or CFU. Its beneficial effects include immunomodulatory properties and an ability to help improve digestive health by strengthening the intestinal barrier and supporting against the inflammatory response by supporting the GI tract. Its really important to maintain good gut health to maintain a high bacterial diversity within our gut, because it’s known that our gut microbiome helps to support our health in a number of ways which include:
- Ensuring efficient absorption of nutrients
- Supports a well functioning immune system
- Promotes good digestion
- A nourished microbiome promotes improved mood
- Supports brain and heart health
If you’re interested in probiotics, you can find out more here.
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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The Gutbrain Axis And Its Relation To Parkinsons Disease: A Review
- 1Department of Epidemiology, College of Public Health and Health Professions & College of Medicine, University of Florida, Gainesville, FL, United States
- 2Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States
- 3Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, United States
- 4Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, United States
What Does Other Research Show About The Vagus Nerve Connection To Parkinsons
Other research has shown an important relationship between the activity of the peripheral vagus nerve and the function of the dopamine system in the brain in rats. Postmortem studies on humans demonstrated that the brain area known as the dorsal motor nucleus of the vagus, which is connected to GI symptoms, was affected in the early stages of PD.The alpha-synucleins are also present in a number of other neurological brain pathologies, such as multiple system atrophy, dementia with Lewy bodies, many cases of Alzheimers, a subtype of essential tremor and others. Perhaps there is a link with the GI tract in these other pathologies.
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Data And Code Availability
The accession number for the C. elegans RNA sequencing data reported in this paper is ArrayExpress: E-MTAB-8164.
The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or upon request.
Code is also available either online where indicated or upon request.
A Bacterial Metabolite From B Subtilis Inhibits
Stress resistance and longevity effects induced by B. subtilis in C. elegans were shown to require live bacteria colonizing the nematodes gut . In our case, these mechanisms seem to be relevant only for the effect of B. subtilis against -syn aggregation in late adulthood and cannot explain the strong protection seen in early adulthood, when no biofilm is present and only insufficient levels of NO are likely available from ingested B. subtilis. To address whether the effects of B. subtilis in early adulthood required live bacteria, we fed -syn-expressing worms dead B. subtilis, killed by a combination of UV and antibiotics. Surprisingly, dead B. subtilis were as protective as live bacteria at day 1 of adulthood .
We next considered whether we could recapitulate the protective effect in the absence of bacteria by supplementing the worms diet with B. subtilis extracts. Nematodes grown from the L1 on an E. coli diet supplemented with B. subtilis crude extracts from either the supernatant or pelleted vegetative cells showed a 17%21% and 21%33% reduction in aggregation, respectively . Therefore, the effect of B. subtilis on -syn aggregation in early adults is partially mediated by the action of an active and stable bacterial metabolite, unlike the short-lived NO, associated with the suppression of aggregation later in life.
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Preclinical Evidence For Probiotic Supplementation In Parkinson’s Disease
Several in vivo animal model studies and cellular model studies have been conducted to evaluate possible neuroprotective effects of probiotics and their potential as a treatment for PD. Among them, murine models were the most widely employed.
Using the genetic MitoPark PD mouse model, Hsieh et al. compared the motor functions of mice with and without probiotic supplementation.46 The control arm was given a sham treatment, while the probiotic treatment arm received a daily mixture of six common probiotic strains . The authors detected better motor performance in the treated animals, which were observed as early as week 16 postsupplementation and persisted until the end of the experiment at week 24. In addition, the treatment group exhibited reduced degeneration of nigral dopaminergic neurons, suggesting a neuroprotective effect of the probiotic mixture.
In an synexpressing worm model of PD, feeding Bacillus subtilis PXN21 resulted in reduced syn accumulation in the host.51B. subtilistriggered alterations of host sphingolipid metabolism were found to be the main mechanism involved in the probioticdriven neuroprotective effect. This finding was in line with increasing evidence in the PD field that an imbalance of lipids, including ceramides and sphingolipids, contribute to PD pathogenesis.52 In addition, the protective effect of B. subtilis was shown to be partly due to biofilm formation in the gut of the worms.51
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.
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What Causes The Tremors Of Parkinsons Disease
The cause of PD is still a mystery, but it is possible that there is a gut-brain connection in PD via at least 2 mechanisms: transmission of prion-like particles up the vagus nerve, and lipopolysaccharide production in the gut.
Related to the first mechanism involving the vagus nerve, many of the effects of the microbiota and/or probiotics on brain function have been shown to be dependent on the activation of the vagus nerve, the long nerve connecting the gastrointestinal tract to the brain. Although not proven conclusively, some scientists believe that in some cases, a problem in the gut travels through the vagus nerve to the brain, leading to PD.
Here is why: Most people have heard about the loss of dopamine neurons in PD cases. However, the hallmark of Parkinsons disease is the presence of clumps of alpha-synuclein, a protein in the brain. Scientists have found alpha-synuclein clumps in other parts of the body, including nerve cells in the gastrointestinal tract. Studies in animal models of PD have shown that clumps of alpha-synuclein in the stomach can travel through the vagus nerve, like proteinaceous infectious particles , to reach the brain. People with severed vagus nerves have a less likely chance of developing Parkinsons disease.
Another common non-motor symptom of PD is depression, which can also have roots in the gut.
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What Is The Microbiome
The human gut harbors trillions of micro-organisms referred to collectively as the microbiome. Current understanding is that the microbiome provides a number of benefits to the human including help with digestion of food, help with warding off harmful microorganisms, aid in the absorption of particular nutrients, and creation of needed vitamins. These functions can influence the nervous system of the gut, called the enteric nervous system . In addition, the gut microbiome releases byproducts and metabolites that have effects on nerves. The microbiome varies from person to person and is influenced by many factors including diet, environment, and genetics. Although no two microbiomes are identical, people with certain diseases may share similarities in their microbiomes.
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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.