New Research on Parkinson’s Disease
New Research on Parkinson’s Disease
Parkinson’s disease (PD) is a progressive nervous system disorder that can take decades to fully manifest. Symptoms often begin with only mild hand tremors but can end with complete disability and sometimes death. Currently PD affects around 10 million people worldwide, and it is on the increase.
As the boomer generation ages out, the prevalence of this disease is rising, since it occurs mostly in those 50 and older. However, as we will see, the seeds of this disease may be planted long before we are 50, so understanding the new research on causes of PD is of value to all of us, not just the elderly. An ounce of prevention and all.
The Second Brain
From a technical point of view, PD is “associated with build-up of alpha-synuclein, a neuronal protein that affects movement”. The bodily structures that are first and most frequently affected by an unhealthy build-up of alpha-synuclein are the enteric nervous system (ENS), which consists of a system of neurons that governs the function of the gastrointestinal tract (i.e. the “second brain”), and the parasympathetic nerves.
Our “second brain”, essentially the neurons lining the gut, contains more neurons than either the spinal cord or the peripheral nervous system. And, the primary gut nerve, the vagus nerve, primarily carries information from the gut to the brain. This influence of the enteric nervous system on mood makes perfect sense, and is why we now look to the gut for its influence on anxiety, depression, autism, and even severe “mental” disorders.
In the past, we looked at PD as being a brain malfunction, but it may well be that those malfunctioning signals are originating far below the first brain, in the second brain.
Thus, recent research has determined that, “gastrointestinal dysfunction is an important non-motor symptom in PD and often precedes the onset of motor symptoms by years. Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve.” (Source)
Butyrate
So, science has established that the gut microbiome impacts brain health, and that people with PD have “gastrointestinal dysfunction”. In fact, “it has been recently demonstrated that PD patients have reduced fecal levels of the potent epigenetic modulator butyrate and its bacterial producers.”
Butyrate is a short chain fatty acid which I have discussed elsewhere (recently here, and, a while ago, here). The long and short of it is SCFAs are produced by fermentation of dietary fiber by certain gut flora.
But for now, we just need to know that SCFAs, and specifically butyrate in this case, are essential for a well functioning gut and healthy microbiome. And, since butyrate is involved in methylating DNA, decreased levels of butyrate are already associated with autoimmune, gastrointestinal, and psychiatric diseases. So, it is a short hop from these ailments to PD, and indeed “decreased levels of bacterially produced butyrate are related to epigenetic changes in leukocytes (white blood cells) and neurons from PD patients and to the severity of their depressive symptoms.”
Repeated research has found that “fecal samples from PD patients have been shown to harbor significantly lower concentrations of the SCFAs acetate, propionate, and butyrate when compared to healthy controls”.
Now, PD is commonly known as “a neurodegenerative disorder that is typically characterized by motor impairments due to the death of dopaminergic neurons located within the substantia nigra pars compacta” (a structure in the “first” brain). However, as mentioned above, one of the recently discovered aspects of PD “is the aggregation of misfolded alpha-synuclein protein in both the central and peripheral nervous system”.
And, the discovery of alpha-synuclein clusters in the enteric nervous system (second brain), along with the observation that PD is accompanied by dysfunction in the gastrointestinal tract “has led to the hypothesis that the pathogenesis of PD may originate in the GI tract or at least outside of the central nervous system”.
This hypothesis further supposes that alpha-synuclein can be transported from the enteric nervous system to the central nervous system through the vagus nerve.
Supporting this theory is the fact that patients who have undergone a vagotomy (cutting the branch of the vagus nerve that tells your stomach to secrete gastric acid) have a decreased risk for developing PD. As well, the “composition and function of the gut microbiome in PD patients have been shown to be significantly different from healthy controls in multiple studies”.
Furthermore, mice bred to overexpress alpha-synuclein, which then develop motor function abnormalities, get even worse if they receive a fecal transplant from someone with PD, compared to receiving a transplant from a healthy donor.
Butyrate, aside from having the ability to inhibit inflammatory cytokine production, and to regulate the immune system, has also been shown to decrease the permeability of the blood-brain barrier (thus protecting the brain), and to relieve anxiety and depression, both of which are common PD symptoms.(Source)
Constipation and Leaky Gut
While the amount of SCFAs produced by the gut microflora are reduced in those prone to PD, such people also show higher than normal levels of these fatty acids in their plasma. This is now assumed to be due to patients with PD having “intestinal wall leakage”, commonly known as leaky gut. This discovery of SCFAs being found in the wrong location (the blood rather than the gastrointestinal tract), was found to be worse in PD patients with chronic constipation compared to those with PD who were not generally constipated.
In fact, the researchers determined that “constipation aggravated gut-blood barrier (GBB) permeability in patients with PD”, concluding that leaky gut made one more prone to PD and constipation made one more prone to leaky gut. (Source)
For those who wish to learn more about how to heal leaky gut syndrome, I suggest reading the following three articles of mine.
Why Would an Arthritis Product Treat Leaky Gut?
How 3 Nutrients Can Heal Most Ailments
Antibiotics
Now let’s look at the study that initiated this newsletter. As we established above, those with PD most often also have a problem with their gut microbiome. Since everyone knows now that antibiotics can disrupt our microbiome in a negative manner, a group of scientists realized that “a potential connection between antibiotic exposure and risk of PD has not been studied previously”.
So, this team set about to do a nationwide study on the subject, and, being Finnish, the nation they chose was Finland. Their study examined 14,000 patients who were diagnosed with PD, and just over 40,000 people who were to be “controls” (those without the disease). They looked at data from 1998 to 2014, including information on individual’s use of orally administered antibiotics during the years 1993 to 2014, and “assessed the association between prior antibiotic exposure and PD”.
The link was pretty strong: “Exposure to antianaerobics and tetracyclines 10 to 15 years before the index date, sulfonamides and trimethoprim 1 to 5 years before the index date, and antifungal medications 1 to 5 years before the index date were positively associated with PD risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics.”
The strongest connection with PD risk was found for oral exposure to macrolides and lincosamides (following the links will give you specific names of these antibiotics)
This research team firmly concluded that exposure to oral antibiotics was strongly associated with increased risk of developing PD, and “the pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to PD.” (Source)
Conclusion
It may well turn out that we have our brain order wrong, and the enteric nervous system should rightly be called the “first” brain, and that thing in our head should be relegated to secondary status.
Nonetheless, the take away from these studies is that we need to consider chronic constipation to be a more serious condition than simply being something that is uncomfortable. And, it is clearly critical that we keep our microbiome healthy and well-fed. All the more important if one has been on repeated courses of antibiotics in their life, as the link to PD seems to hold true even if the repeated antibiotic use was years in the past.
I would assume this is because the average person never fully counteracts the damage that a round of antibiotics does to their microbiome by giving it the food (prebiotics and probiotics) it requires to get back to its ideal state following antibiotic use.
At this point I will suggest one consider using our products that support a healthy microbiome. For day-to-day maintenance of the microbiome one can use Lactospore, or for more serious concerns, such as IBS, one can use the more powerful version (5 times stronger), Lactospore Supreme.
But for those seriously concerned about their risk of developing PD due to excessive antibiotic use, I would have to recommend using our Provide Smoothie Mix, which is designed specifically to support the gut/brain axis. This formula includes Lactospore along with the cutting edge prebiotic hydrolyzed guar gum, and Lion’s Mane mushroom, which has been proven to support both the microbiome and the brain.