PARKINSON’S DISEASE’ INTIMATE RELATIONSHIP TO GUT HEALTH
(DYSBIOSIS AND INTESTINAL PERMEABILITY)
“The hypothesis being advanced in this paper is that there is a new medical paradigm emerging from the biomedical research carried out in this century… The main idea is that there is a common pathway from wellbeing and health to chronic disease and even to death, which comprises the following steps:
1) unhealthy diet, sedentary life style and permanent exposition to xenobiotics [chemicals] and all kinds of noxious stimuli
2) intestinal dysbiosis
3) alteration of the intestinal mucus layer (especially that of the colon)
4) disruption of the endothelial tight junctions [3,4, and 5 all pertain to leaky gut / increased intestinal permeability]
5) metabolic endotoxemia+bacterial translocation
7) exacerbation of the enteric nervous system (ENS) and consequent maladaptation and malfunctioning of the colon
8) epigenetic manifestations
9) premature death.
In order to maintain a good health or to improve or even reverse chronic diseases in a person, the main outcome to look for is a homeostatic balance of the intestinal microbiota (eubiosis), most of which is located in the colon. The following facts about intestinal microbiota are nowadays generally accepted: there are about 10 times more bacteria in the gut than human cells in every human being; the microbioma is about 100-150 times bigger that the human genome, and there is a clear link between intestinal microbiota and many of the most common chronic diseases, from obesity and diabetes to depression and Parkinson disease and different kinds of cancer. The main implication of this theory is that we should become a sort of microbiota farmers, that is, we ought to be more conscious of our intestinal microbiota, take care of it and monitor it permanently. Thus, as part of our good life habits (healthy eating, physical exercise), we should probably undergo periodic seasons of fasting and colon cleansing, as it was common in older times.”
“Microbiota farmers“! Let me paint you a picture of what I looked like after reading this. I was staring at the screen, with my mouth agape in drop-jawed wonder. Reading a medical study by five mainstream researchers about the consequences of a LOSS OF GUT HOMEOSTASIS was nothing short of amazing! I felt vindicated. Mostly because one short month before this study was published, I gave my readers THIS POST (The Gut / Microbiota / Brain Axis: Most Disease States are Different Manifestations of the Same Underlying Dysfunctions), after coming to similar conclusions myself.
Here’s what’s so cool about knowing that most disease has a “common cause”. If underlying causes of all disease states really are this similar, then solutions should likewise be similar. They are, and it is! That’s why this information is so valuable to you whether you have Parkinson’s or Dippsy-Doodleitis — or for that matter, have not (yet) been diagnosed with any disease. Whatever you are doing medically / pharmaceutically; you are going to follow a SIMILAR PROTOCOL as far as addressing the DIY side of your chronic illnesses is concerned. Honestly, if we ended this post here, you would have already gotten way more than your money’s worth. But since we’re just getting started, strap yourself in and enjoy the ride.
Let me first show you the early stages of autoimmunity — the two sides of Gut Dysfunction; LEAKY GUT SYNDROME & DYSBIOSIS. In the first, the “tight junctions” between the cells that make up the Gut’s lining (epithelial barrier) become ‘loose,’ allowing nasty things into the bloodstream that shouldn’t be there (PARASITES, partially digested food fragments, bacteria, FUNGUS, etc, etc). When this happens the Gut is said to be “leaky,” which the medical community refers to as ‘intestinal barrier hyper-permeability‘ or something similar. The second side of the coin refers to an imbalance in the Gut’s natural flora (MICROBIOME), which is known as “Dysbiosis”. Be aware that this is a chicken / egg situation, meaning that either one can occur first, leading to the other. In May of last year a dozen researchers from Chicago’s Rush University Medical Center showed this process in action via a study published in the Journal of Parkinson’s Disease (The Potential Role of Gut-Derived Inflammation in Multiple System Atrophy).
“Recent evidence suggests that Parkinson’s disease is associated with intestinal microbiota dysbiosis, abnormal intestinal permeability, and intestinal inflammation. This proof-of-concept study provides preliminary evidence that like Parkinson’s Disease, Multiple System Atrophy subjects display evidence of disrupted intestinal barrier integrity, increased marker of endotoxin-related [lipopolysaccharide] intestinal inflammation, and pro-inflammatory colonic microbiota.”
This is where it’s at folks, and is true of almost all Autoimmune Diseases, as well as MSA (Multiple System Atrophy). What is Multiple System Atrophy you ask? Characterized by the same tremors, slow movements, rigid muscles, and postural instability as Parkinson’s Disease, MSA tends to have more ANS (Autonomic Nervous System) symptoms — in most cases, those of SYMPATHETIC DOMINANCE (click the link for some hints on how to tone down SD), although it can be parasympathetic. Follow along as I take you through a number of studies, none published earlier than 2017, in no particular order.
In April of last year, twenty Russian researchers published a study (Analysis of Gut Microbiota in Patients with Parkinson’s Disease) in the Bulletin of Experimental Biology and Medicine, saying that “The human body is now viewed in the context of its symbiotic relationships to microbiota, an ensemble of bacteria, viruses, protozoa, fungi, and archaea colonizing all body biotopes (skin, gastrointestinal tract, airways, and urogenital system). Growing evidence appears on the potential role of microbiota in the pathogenesis of human diseases, in particular nervous system disorders. Microbiota is as an important part of the body. On one hand, its content is partly stipulated by human genotype and regulated by immune mechanism, on the other, it depends on environmental conditions including nutrition and ecological situation in the habitat.” In English, this means that even though you might carry the genes for who-knows-what, it’s the “environment” (habitat, diet, exposure to CHEMICALS and POLLUTANTS, rejection, jealousy, hatred, etc, etc) that turn the genes on and causes them to express various disease states). This is known as EPIGENETICS and is more important than genetics — far more important.
In May of last year, the journal Parkonsinism and Related Disorders (Gut Microbiota: Implications in Parkinson’s Disease) came to a number of interesting conclusions as well. Listen to these sentences strung together from throughout the study. “80% of PD patients suffer from constipation. Additionally, PD constipation is associated with α-synuclein accumulation and neuro-degeneration in the enteric nervous system, with increased local inflammation, oxidative stress, and intestinal permeability. The prevalence of H. Pylori infection is high among PD patients and causes motor impairments by hindering the absorption of levodopa, a primary drug for PD management. Similarly, SIBO has been associated with PD too. SIBO affects nearly one-quarter of PD patients and was associated with motor impairments.” OXIDATIVE STRESS is super common in autoimmunity along with GUT INFLAMMATION. The authors went on to talk about treatment methods, having sections on ANTIBIOTICS, PROBIOTICS, and even my favorite; FMT (FECAL MICROBIOTA TRANSPLANTS). The problem with antibiotics is that they are arguably the biggest cause of dysbiosis to begin with, and as for probiotics, click the link to see why they are not always what they are cracked up to be. Interestingly, these authors also linked INFECTIONS other than what I mentioned (H. PYLORI) to PD.
In November of last year, the European Journal of Neurology (More Than Constipation: Bowel Symptoms in Parkinson’s Disease and Their Connection to Gut Microbiota) said that, “The majority of Parkinson’s disease patients suffer from gastrointestinal symptoms of which constipation is considered the most prominent. Recently, in addition to constipation, a diagnosis of irritable bowel syndrome (IBS) was also found to be associated with increased PD risk. Gut microbiota alterations have been reported in IBS and recently also in PD. Symptoms that were IBS-like were significantly more prevalent in PD patients than in controls.” How much more prevalent? Almost 100% higher in those with PD. For the record, IBS is itself an Autoimmune Disease that is strongly associated with both SIBO (Small Intestinal Bacterial Overgrowth) and FODMAPS (HERE).
Just a few short months ago, in December of 2017, seventeen researchers published this study (Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease) in Cell, concerning Parkinson’s relationship to a neuronal protein known as α-SYNUCLEIN.
“Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson’s disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites [short chain fatty acids — SCFA] to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice, and suggest that alterations in the human microbiome represent a risk factor for PD.”
The English version: Even in mice that were genetically raised to express high levels of α-synuclein; that alone did not cause the neurological symptoms (motor deficits) seen with Parkinson’s until dysbiotic bacteria were added to the equation. This, folks, is epigenetics in action. Thus, antibiotics rendered at the correct stage of the disease process improved the situation. Likewise, colonizing or re-colonizing the Gut with FMT-derived dysbiosis caused symptoms. Furthermore, when certain SCFA’s were introduced to germ-free mice, it was enough to cause symptoms (for the record, SCFA’s are not all bad. Some, such as butyrate are the primary food sources for “good” bacteria, having both anti-inflammatory and anti-tumor properties). What’s amazing (but not surprising if you’ve followed my posts on FMT) is that when feces from people with Parkinson’s was put into the hyper-αSyn mice, the mice developed motor deficits “movement disorders“. And as for microglia activation (brain inflammation), you can read about that HERE. Bottom line, no matter what other factors might be present, if the right bacteria are not there, the chances of developing Parkinson’s decrease dramatically.
Speaking of SCFA’s, a study from the November issue of Parkinsonism & Related Disorders (Short Chain Fatty Acids and Gut Microbiota Differ Between Patients with Parkinson’s Disease and Age-Matched Controls) showed exactly what I was just talking about. “Patients with Parkinson’s disease frequently have gastrointestinal symptoms and exhibit the PD-typical pathohistology in the enteric nervous system (ENS). Both, clinical symptoms and pathohistological changes in the ENS occur at early stages and can precede the motor manifestations of PD.” Did you catch that? Problems in the Gut’s nervous system (the ENS) manifest before the tremors, weakness, and altered gait. The neurological changes were associated with “Fecal SCFA concentrations that were significantly reduced in PD patients compared to controls.” In other words, these folk’s Gut bacteria were not making enough BUTYRATE. “Our study confirms the recently reported association between PD and the abundance of certain gut microbiota and shows a reduction in fecal SCFA concentrations (one main metabolic product of certain gut bacteria). The reduction in SCFA might, theoretically, induce alterations in the ENS and contribute to gastrointestinal dysmotility in PD.”
In November of last year, PLoS One gave us an interesting piece of research from Japan (Progression of Parkinson’s Disease is Associated with Gut Dysbiosis: Two-Year Follow-Up Study). Knowing that microbiomes of those with diseases always show less diversity (fewer microbial species), what would you expect to see over the course of patients living two years with Parkinson’s? “Emergence of intestinal α-synuclein… in presymptomatic PD patients implies that the PD pathology starts from the intestine. We and others indeed reported intestinal dysbiosis in PD patients. In 2 years, total fecal bacterial count, as well as the counts of 6 out of 10 representative intestinal bacterial groups/genera/species, were decreased in all PD patients.” This should make you start wondering what you could possibly do to increase your number of bacterial species (not just the gross numbers of a few bacterial species as happens with probiotic therapy).
October’s issue of Neurology (REM Sleep Behavior Disorder is Related to Enteric Neuropathology in Parkinson Disease) showed why many of you with Parkinson’s (or those who might be more prone to developing Parkinson’s at some future time) have trouble sleeping. When it comes to “enteric neuropathology” — pathology of the Gut’s nervous system — “Patients with PD and REM sleep behavior disorder (RBD) have a greater frequency of synuclein pathology in the enteric nervous system, suggesting that RBD is associated with widespread synuclein neuropathology.” If you recall, Parkinson’s is intimately related to issues with α-synuclein. A year ago this month, Frontiers in Neurology published A STUDY on the well-researched and much-written-about relationship between PD and sleep disturbances.
April’s issue of Current Pharmaceutical Design (Gut Permeability and Microbiota in Parkinson’s Disease: Role of Depression, Tryptophan Catabolites, Oxidative and Nitrosative Stress and Melatonergic Pathways) covered a wide variety of topics, including the “leaky” Gut and Dysbiosis. “These wider biological changes in PD are compatible with alterations in gut permeability and changes in gut microbiota.” Although this study was essentially a quest for a new drug, there were interesting facts to be gleaned on both SEROTONIN and MELATONIN as related to PD. A study from April’s issue of the European Journal of Neuroscience showed via its title that a leaky barrier system (what I usually refer to as “THE LEAKIES” — leaky brain, leaky cord, leaky lung, leaky nerve, etc) is not something that only happens in the Gut (In Vivo Bioluminescence Imaging of Neurogenesis – The Role of the Blood Brain Barrier in an Experimental Model of Parkinson’s Disease). Still another study, this one from last February’s copy of Biomacromolecules (Iron Chelation Nanoparticles with Delayed Saturation as an Effective Therapy for Parkinson Disease) showed how the substantia nigra gets gummed up with iron, and how scientists have come up with a potential CHELATING AGENT to remove it (zwitterionic poly 2-methacryloyloxyethyl phosphorylcholine), causing a substantial reduction of PD symptoms.
November’s issue of Current Behavioral Neuroscience Reports (Microbes Tickling Your Tummy: The Importance of the Gut-Brain Axis in Parkinson’s Disease) concluded that “Evidence suggests an important role of the gut-brain axis in PD pathogenesis. These interactions might be essentially influenced by the gut microbiota. Besides the well-known motor deficits, PD patients very often suffer from non-motor symptoms including hyposmia [trouble smelling], anxiety, depression, impaired executive function, and most commonly gastrointestinal dysfunction. Some of these symptoms are very often present in pre-clinical stages, and their occurrence in healthy individuals is associated with an increased risk of developing PD. PD patients exhibit a pro-inflammatory microbiota profile that might cause and increase in gut permeability, allowing leakage of bacterial products and inflammatory mediators from the intestines [into the systemic circulation]“. It’s all there folks. The question is whether or not people have the ability to change their microbiomes? Stick around because I’ll answer that momentarily.
The March 2017 issue of Cerebrum (Gut Feelings on Parkinson’s and Depression) talked about both the HPA-AXIS as well as the Brain-Gut Axis. “What we’ve learned is that what is commonly referred to as “the brain-gut-microbiota axis” is a bidirectional system that enables gut microbes to communicate with the brain and the brain to communicate back to the gut. It may be hard to believe that the microbes in the gut collectively weigh around three pounds—the approximate weight of the adult human brain—and contain ten times the number of cells in our bodies and over 100 times as many genes as our genome. Over the past few years, the gut microbiota has been implicated in developmental disorders such as schizophrenia and autism, neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease, mood disorders such as depression, and even addiction disorders. It now seems strange that for so many decades we viewed the gut microbiota as bacteria that did us no harm but were of little benefit. This erroneous view has been radically transformed into the belief that the gut microbiota is, in effect, a virtual organ of immense importance. It is conceivable that PD occurs because of toxins produced by the gut microbiota or because of a failure to produce key essential neuronal dopamine specific nutrients, which are required by dopamine producing cells. The microbiota that we initially develop is determined by the mode of birth delivery of the infant (vaginally or by caesarean section), diet, and exposure to antibiotics.” This is why much of the underlying pathogenesis of AUTISM is not really so different than that of PD (click the link and scroll titles to see what I mean). And as for ALZHEIMER’S and DEPRESSION, we see something similar as well.
A Norwegian study from July’s issue of Medical Hypotheses (Parkinson’s Disease; The Hibernating Spore Hypothesis) showed something amazing about BLACK MOLD and other forms of dysbiosis. “In accordance with Broxmeyer’s  hypothesis and supported by the evaluation above, PD may be due to reactivation of spores, either fungal or bacteria, in the brain – perhaps involving some form of mold, or more likely – endospores from an Actinomycete. At present, this explanatory model is perhaps the most feasible hypothesis regarding a causative agent in PD.” Actinomycetales are a type of bacteria. For those of you on Dr. Eric’s board, it seems that “Crazy Karim” has probably been right all along!
Last month’s issue of the Journal of Neurogastroenterology and Motility (Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson’s Disease: A Critical Review) showed that we might be getting to the point where early diagnosis of PD via metabolic biomarkers (in this case “calprotectin, alpha-1-antitrypsin and zonulin“) might actually be possible. “Early diagnosis should enable immediate treatment and help protect the neuronal functions, slow disease progression, improve patient’s quality of life and ultimately reduce the overall cost of PD treatment.” Great, but truthfully early diagnosis doesn’t mean jack if you don’t deal with the underlying epigenetic causes! Just remember, BIG PHARMA isn’t interested in a full-blown cure; they are looking for drugs to manage your problem — drugs you’ll have to take for the rest of your life. All too often it’s how EVIDENCE-BASED MEDICINE rolls. Need proof?
Firstly, a collaboration from researchers from across the United States showed in the May 2017 issue of Movement Disorders (Parkinson’s Disease and Parkinson’s Disease Medications have Distinct Signatures of the Gut Microbiome) that, as the title suggests, “PD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome.” What’s interesting is that DR. ART AYERS was talking about this phenomenon with both nutrients and drugs as related to diseases in general years ago. And secondly, why might it be better to deal with this problem via microbiome intervention than by pharmaceutical intervention?
A study from the November 2017 issue of Scientific Reports answers this question with their study, Levodopa-Induced Abnormal Involuntary Movements Correlate with Altered Permeability of the Blood-Brain-Barrier in the Basal Ganglia. “Chronic levodopa treatment leads to the appearance of dyskinesia in the majority of Parkinson’s disease patients.” What is levodopa (usually called L-Dopa)? It’s the drug used to replace the dopamine that is not being made because the substantia nigra portion of the brain’s basal ganglia is messed up. What’s critical to remember is that these conclusions were not news when the 1994 issue of Clinical Neuropharmacology (Problems With Long-Term Levodopa Therapy for Parkinson’s Disease) made this statement a quarter century ago — about something they had known about for a quarter century.
“The introduction of levodopa 25 years ago revolutionized the management of Parkinson’s disease. However, it soon became apparent that the drug offered only symptomatic relief and did not affect the underlying pathology. Moreover, chronic use of the drug was associated with a range of adverse effects. After 5 years the majority of these patients suffer fluctuations, dyskinesias [abnormal, uncontrolled or involuntary movements], toxicity, or loss of efficacy. As the disease progresses, new disabilities appear that are less responsive to levodopa, and its efficacy can appear to diminish, with increased doses often leading to toxicity.“
Look, the point of mentioning this last study is not to pick on those of you struggling with Parkinson’s who have taken medication. PD is the definition of being between a rock and a hard place. However, what I’ve shown you today, along with what I’ve shown you in the past, might leave you able to dent Parkinson’s armor just enough so that at the very least, you might be able to get by with less medication. Let me give THOSE OF YOU struggling not only with PD, but with autoimmunity in general, a small example of what I mean.
Once you understand the strong scientific link between PD and both GLUTEN & SUGAR (blood sugar always fuels dysbiosis — HERE), you’ll start to see why some of my recommendations make sense. In fact, I know people — lots of people — who are kicking the living #$^% out of their autoimmune diseases by following some of the ideas found in THIS POST. Sure, you might require some personalized / customized FUNCTIONAL MEDICINE, but as far as a starting point that won’t cost you anything and won’t make things worse, I’m not sure you can do better. Leverage the information in today’s post to start creating your own EXIT STRATEGY, and do it today.
Allow me to finish by making a simple, but important point. Educate the next generation (your children, grandchildren, nieces, nephews, etc) who are likely carrying the same genetic makeup you are. Use your knowledge of epigenetics to help them start making the necessary changes today as well — because frankly, things get way tougher once you are diagnosed, no matter how early that diagnosis comes.