Sunday, August 7, 2022

Gut Bacteria And Parkinson’s

Pd Patients Have Higher Calprotectin And Lower Scfa Levels In Stool And Lower Cxcl8 Levels In Plasma Compared To Controls

Caltech Researchers Link Parkinsons Disease to Gut Bacteria

Patient and control groups were similar with regard to basic demographics such as age, sex, and body mass index however, as we knew from previous analyses of the same subjects , the groups differed regarding medications, medical history, and various symptom scores. A higher percentage of controls reported a history of stroke and use of medications for high blood pressure and cholesterol, and PD patients scored higher on scales of non-motor symptoms, gastrointestinal problems, and constipation . Contrasting inflammatory markers and SCFAs between PD patients and control subjects, patients had lower levels of butyric and propionic acid and higher levels of calprotectin in their stool and lower levels of CXCL8 in plasma . When the data were stratified by sex, the differences were particularly prominent for butyric acid in males and for plasma CXCL8 and stool calprotectin in females . For calprotectin, this sex effect may be explained in part by relative baseline levels of the protein. Among control subjects, calprotectin levels trended lower in females than in males .

Table 1 Demographic and Clinical Details of Subjects

Key findings from this study are summarized in Additional File .

Effect Of Medication On Gut Microbiota

Most of the previous studies including PD patients with advanced and treated with L-DOPA which affects colonic motility and may promote intestinal bacterial overgrowth . To avoid alterations of gut microbiota related to late-stage PD or l-DOPA-induced intestinal effects, we included 7 untreated naive PD patients with early stage. In the present study, the naive PD patients had significant abundance of Bifidobacterium, and lactic acid bacillus compared with control group. Supporting our results Bedarf and colleagues found that early, l-DOPA-naïve PD patients carried an altered gut microbiota composition. Weis and colleagues found that the relative abundances of the bacterial genera including Bifidobacterium, and Enterococcus, were significantly influenced by medication with l-dopa and entacapone, respectively . This study was performed on fecal samples of naïve 34 PD patients and followed up 3 months after medication.

Interestingly, there was no significant difference between treated and untreated except in Akkermansia as it is more abundant in treated than non-treated patients. Constipated individuals have been shown to have a gut microbiome enriched in Akkermansia , and constipation is one of the major non-motor symptoms in PD. As a number of medications used to treat PD can cause constipation so the abundance of Akkermansia in treated patients may be related to both medication and chronicity of disease-related constipation.

Parkinsons Disease And The Gut

In Part 1 of this 3-part blog I cover questions or concerns that many of my patients with Parkinsons disease have that center around the gut.

  • Constipation/delayed gastric emptying
  • Dietary recommendations for PD in general
  • Protein interactions with levodopa
  • Dietary interactions with MAO-B inhibitors
  • Connection of PD and the gut
  • Antibiotic impact on gut bacteria
  • The outlook for prevention or prevention progression for PD
  • 1. Gastrointestinal symptoms of Parkinsons disease

    Up to 70% of patients with PD have gastrointestinal symptoms, often beginning years prior to the onset of motor symptoms, along the entire length of the gastrointestinal tract. I will describe the issues that can arise from top to bottom, so to speak.

    Symptoms of the mouth and throat include the slowing down and reduction of the swallow response, resulting in drooling or repeated swallows being required in early stages of PD. As the disease progresses, swallowing difficulty may worsen, resulting in aspiration , which can be silent or associated with coughing, choking, or pneumonia. Dysphagia and aspiration should be evaluated by a swallow study, performed by a speech therapist. Treatment recommendations include chewing more slowly, clearing ones throat before taking another bite, eating while sitting up with the chin tucked, and changing the texture of the solids and liquids to be easier and safer to swallow.

    For more on management of constipation, please see Part 2 of this blog.

    • Green leafy vegetables

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    But How Does A Bad Microbiome Produce Parkinsons

    A 2017 study has revealed at least one of the major reasons why the gut microbiome can produce Parkinsons. Researchers from the University of Alabama at Birmingham tested 197 Parkinsons disease patients along with 130 healthy control subjects. To offset for local diets, the study tested people from the South, people from the Northeast and people from the Northwest. The researchers tested each persons gut bacteria and analyzed the different species that populated each persons gut.

    The findings were eye-opening.

    First, the study once again established that Parkinsons disease patients have abnormal populations of gut bacteria compared to healthy people. But it was the particular species of bacteria that became the most revealing aspect. Dr. Haydeh Payami, a neurology professor in the school of medicine at the University of Alabama explained:

    Our study showed major disruption of the normal microbiome the organisms in the gut in individuals with Parkinsons.

    The researchers found that probiotic species that are involved in helping the body remove toxic chemicals from the body were glaringly low among the Parkinsons disease patients. Probiotic families at lower levels included:

    Bifidobacteriaceae Pasteurellaceae Verrucomicrobiaceae

    This is significant. Why? Because other research has linked Parkinsons disease to the exposure of chemicals in pesticides and other consumer products.

    How Your Support Made This Research Project Possible

    Parkinson

    Appel-Cresswells new project builds on earlier research to study the fungal microbiome, a project Parkinson Canada supported. That was one of the grants that then facilitated a whole lot more work, she says.

    Its really the seed funding, particularly with these pilot grants, that allows us to go way beyond that. Its the necessary start to any of these projects.

    Seed or pilot grants allow researchers to leverage funding from other sources.

    You have to start somewhere, and that is the seed that is planted and has really grown into a whole program that is very interconnected and makes use of all these synergies between all these fields, she says.

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    Microbiota As Current Therapeutic Approaches To Pd

    Till now, no therapeutic approach has been found that have a beneficial effect on PD pathophysiology. Modifying the existing microbiota to maintain the intestinal homeostasis by various microbiota-targeted interventions, such as antibiotics, prebiotics, probiotics, synbiotics or fecal Microbiota Transplant are current therapeutic approaches under consideration . We have discussed how these interventions have been shown to favourably affect gut homeostasis and the

    Uncovering The Parkinsons Gut Bacteria Link

    Since the early 1990s, medical science began to link Parkinsons disease with gut conditions. Back then, researchers from the University of Nebraska Medical Center published a paper in the medical journal Neurology after finding numerous Parkinsons cases among those with gastrointestinal issues, including constipation, nausea, gut inflammation, acid reflux and other GI issues.

    You see, the researchers knew these were all symptoms of abnormal gut bacteria.

    Continuing clinical examinations of Parkinsons patients at the University of Nebraskas Medical Center found that the motor conditions related to Parkinsons disease also correlated with problems with the vagus nerve, the rectum and the pelvic floor.

    The vagus nerve runs from the brain to the gut.

    These studies also identified dopamine receptors within with lower esophageal sphincter which opens and closes the stomach to food.

    Fast-forward another decade. In 2011, research from the University of Tennessee Health Science Center picked up this association between Parkinsons and the gut. They found additional correlations with digestion, salivation issues and rectum problems, along with the other symptoms found earlier.

    The research also discussed a condition called gastroparesis where the stomach doesnt empty properly.

    As GI problems like these began to become increasingly associated with gut issues, the search turned to whether Parkinsons may be associated with problems with gut bacteria.

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    Dietary Interventions To Slow And Improve Parkinsons Symptoms By Restructuring The Gut Microbiome And Decreasing Inflammation

    Study Rationale:There is a link between the gut and the brain in Parkinsons disease , and gut bacteria may play an important role. Gut bacteria they affect the bowel mucus barrier, produce poisonous chemicals, and stimulate inflammation. People with PD can have changes in gut bacteria with an increase of potentially bad bacteria. These changes may contribute to symptoms such as severe constipation and may play a role in progression of the disease through increased inflammation. Special diets, like fiber-rich diet or addition of resistant starch , support a healthy microbiome in the gut. Therefore, healing the gut microbiome might improve symptoms and quality of life in people with PD and may even slow disease progression.

    Hypothesis:Special diets rebuild the gut microbiome and decrease inflammation in people with PD. This leads to improved symptoms, raises quality of life and might even slow disease progression.

    Study Design:We will separate study participants with PD into three dietary groups. Either they stick to their usual eating habits they change to a high-fiber/vegetarian diet or they add resistant starch to their main meals. We will take stool samples to measure the gut microbiome and blood samples to measure inflammation. We will document signs of PD as well as quality of life. This main part of this pilot study will take two weeks. For some participants, we will extend the study to one year to evaluate impact on disease progression.

    Gut Bacteria Could Guard Against Parkinson’s Study Finds

    Webinar: “Gut Bacteria and Parkinson’s” January 2017

    A common bacteria that boosts digestive health can slowand even reversebuild-up of a protein associated with Parkinson’s, new research suggests.

    Building on previous research linking brain function to gut bacteria, this study in a Parkinson’s model of roundworms, identified a probioticor so-called good bacteriawhich prevents 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 probiotics impact the condition.

    In the brains of people with Parkinson’s, alpha-synuclein protein misfolds and builds up, forming toxic clumps. These clumps are associated with the death of nerve cells responsible for producing dopamine. The loss of these cells causes the motor symptoms associated with Parkinson’s, including freezing, tremors and slowness of movement.

    The researchers from the Universities of Edinburgh and Dundee used roundworms altered to produce the human version of alpha-synuclein that forms clumps. They fed these worms with different types of over-the-counter probiotics to see if bacteria in them could affect the formation of toxic clumps.

    “Changes in the microorganisms in the gut are believed to play a role in the initiation of Parkinson’s in some cases and are linked to certain symptoms, that’s why there is ongoing research into gut health and probiotics.

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    Early Satiety And Bloating

    Early satiety and bloating are due to impaired gastric emptying with magnetic resonance imaging and electrogastrography showing gastric motility abnormalities . Loss of neuronal function within the myenteric plexus and LB inclusions embodied within the vagus nerve slowing down intestinal peristalsis may cause these abnormalities . Gastroparesis could have implications involving absorption of L-Dopa and thus influence the degree of motor symptoms , whilst small bowel dysmotility may cause abdominal bloating and predispose to small intestinal bowel overgrowth .

    Gut Bacteria Could Guard Against Parkinsons

    New research suggests that a bacteria which boosts digestive health can slow and even reverse the build-up of a protein associated with Parkinsons.

    Researchers from the Universities of Edinburgh and Dundee have identified a probiotic or so-called good bacteria which prevents the build-up of a protein which is linked with Parkinsons. In people with Parkinsons, alpha-synuclein protein builds up and forms toxic clumps which are associated with the death of dopamine producing nerve cells. The loss of dopamine is what causes motor symptoms in Parkinsons.

    Using roundworms, scientists found that a probiotic called Bacillus subtilis could not only protect against the build-up of this protein, but can also clear some of the already formed protein clumps.

    These new findings could pave the way for future studies that gauge how supplements such as probiotics impact Parkinsons.

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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 (

    The Influence Of Environmental Risk Factors On Gut Microbiota

    Parkinson

    An important issue in the present study was that the control group were recruited from relatives of our patients with nearly same age- and sex-distribution in order to limit any differences in diet, residency, job, water source, pesticide exposure, and daily intake of fluid and water, or fruits as confirmed by the absence of significant differences between PD patients and controls in any of these items. Our findings showed that there was a significant association between pesticide exposure and Bifidobacterium levels in patients with PD, which is higher in non-pesticide exposed patients than pesticide-exposed patients . Our data with Hill-Burns and colleagues who found that there is may be a correlation secondary to long-standing exposure to pesticide/herbicide contaminant in stream and ground water and the increased activity in PD of pathways that degrade xenobiotics.

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    Can An Altered Microbiome Contribute To A Diagnosis Of Pd

    Research studies in animals have shown that an altered microbiome might contribute to PD pathology. For example, one study showed that in a mouse model of PD that overexpressed alpha-synuclein, there was more alpha-synuclein accumulation in the brain of the mice with an intact microbiome as compared to the same mice who were raised in a germ-free environment with no bacteria in their gut. This supports the theory that abnormal alpha-synuclein accumulation in the brain is enhanced by a particular microbiome in the gut.

    Other studies showed that transplantation of fecal material from PD mice to normal mice, thereby introducing a PD microbiome into mice without PD pathology their brain, led to impairment of motor function and a decline in brain dopamine. These studies also support the theory that a particular microbiome might be integral in causing PD pathology in the brain.

    Metabolites By Intestinal Bacteria

    Intestinal bacteria produce SCFAs, as well as vitamins B2, B6, B12, and K, folic acid, pantothenic acid, biotin , serotonin, and polyamines. Serotonin promotes intestinal peristalsis. Intestinal SCFAs are decreased in PD . Serum polyamines are also decreased in PD . We will focus on the roles of SCFAs and polyamines in this communication.

    Fig. 3.

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    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.

    Parkinsons And Gut Health

    Parkinson’s and Gut Bacteria: Digest a Cure?

    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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    Gut Microbiota Alterations In Pd Pathology

    Emerging pieces of evidence suggest the link may exist between the intestinal microbiota and PD pathophysiology, have sparked increasing attention. Clinical studies have demonstrated that most of the PD patients suffer from various severe GI symptoms. Numerous studies have shown the altered gut microbiota composition in PD. One recent study has found the high prevalence of Helicobacter pylori infection in patients with PD, which impair the intestinal L-DOPA absorption, a

    The Gut Microbiome In Parkinson’s: Species Level Resolution And Function

    Although Parkinsons disease kills brain cells that affect our ability to move and to reason, the trillions of micro-organisms living in our gastrointestinal tracts may be important contributors to the illness.

    At the University of British Columbia and with her colleagues at the University of Calgary, Dr. Silke Appel-Cresswell, a neurologist and associate professor, uses high-resolution screening tools to study the bacteria in the guts of people with Parkinsons. This colony of bacteria, fungi and viruses is known as the microbiota.

    Appel-Cresswell is pinpointing the particular strains of bacteria driving inflammation or allowing too many toxic proteins to move from the gut to the brain.

    From the evidence we have so far, it really seems that the microbiota in people with Parkinsons are different from those in people who do not have Parkinsons, she says.

    If particular strains of bacteria cause inflammation, for example, it could trigger the body to mount a too-aggressive immune response. This could also lead to the accumulation of the protein alpha-synuclein, damaging brain cells, including those that produce dopamine. Lack of dopamine-producing cells causes the stiffness, tremors and difficulty walking that characterize Parkinsons disease.

    From the evidence we have so far, it really seems that the microbiota in people with Parkinsons are different from those in people who do not have Parkinsons.

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    Research Subjects Sample Collection And Ethical Issues

    The study participants consisted of 20 PD patients and 20 healthy controls. PD patient were recruited from the patient material of the Neurology Outpatient Clinic of Terveystalo Healthcare, Kamppi, Helsinki. The control group consisted of 10 spouses and 10 non-spouses of PD patients. As a prerequisite, selected PD patients had to fulfill the clinical features of the UK Parkinsons Disease Society Brain Bank diagnostic criteria . Furthermore, PD patient disease progression was scored using the Hoehn and Yahr scale as an estimate of the clinical stage of PD . Symptoms or signs of parkinsonism were exclusion criteria for the controls. Exclusion criteria for both groups included cognitive disturbance and a history of antibiotic use within 3 months prior to the date of fecal sampling. Fecal samples were collected by donors in sealed polypropylene containers and subsequently frozen and stored at -75°C until further analyses. The study was approved by the Ethics Committee of Helsinki and the Uusimaa Health District area of Finland, and all procedures were in accordance with the relevant regulations. Each study participant also provided written informed consent.

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