Two New Articles on Parkinson’s
Posted on May 28, 2019
Two more recent article provide yet more evidence linking gut inflammation to the development of Parkinson’s disease…which my regular readers know, is another of my particular interests, as I have 3 friends already suffering from it.
The first article describes research at the University of Wisconsin.[i] Like humans, monkeys with inflamed bowels also show “…chemical alterations similar to abnormal protein deposits in the brains of Parkinson’s patients, lending support to the idea that inflammation may play a key role in the development of the degenerative neurological disorder.” That is, they found the same kind of abnormal (folded protein), alpha-synuclein, that appears in people. I’ve written about this several times, like here.
No one yet knows for sure all the functions of alpha-synuclein, but it is found in all neurons. It’s thought to play a role in both the immune system and (mainly) in the central nervous system. In Parkinson’s, for reasons not yet understood, it changes shape and clumps together into masses called Lewy bodies. When James Parkinson first described the disease in 1817, he also noted that those suffering from it had gastrointestinal issues. In fact, people with inflammatory bowel diseases are more likely to be diagnosed with Parkinson’s. It’s been known for many years that inflammation and oxidative stress are likely culprits in the development of the disease.
The fact that the same findings also happen in a completely different species provides yet more confirmation that inflammation in the gut is the primary cause.
The question then, of course, becomes – what is the root cause of this inflammation of the gut tissue? Dysbiosis of the gut microflora looks more and more likely to be the prime suspect. I looked through a just-published review of what we know/don’t know about the microbiome in PD out of the University of Washington, and found a few interesting highlights to share:[ii]
- There are fairly well document microbiome abnormalities in PD. They not only have different gut bacteria, but the kinds they have are associated with having motor issues in walking, standing, and so forth. They also have low levels of anti-inflammatory short chain fatty acids, which are produced by good gut bugs. And a leaky gut/leaky brain may explain be the trigger for that abnormal alpha-synuclein: “In a recent study, researchers looked at the relative abundance of Enterobacteriaceae in patients with PD and found that (1) patients had higher levels of these bacteria relative to healthy controls, and (2) the abundance of this family was positively associated with severity of postural instability and gait difficulty. (Analysis of fecal samples from patients with PD reveal decreased proportions of certain species of bacteria like Faecalibacterium prausnitzii as well as decreased levels of the SCFAs acetate, propionate, and butyrate…SCFAs are generally associated with maintaining the blood-intestinal and blood-brain barriers and are one of a select few substances that can cross the blood-brain-barrier. Decreased levels of SCFAs, as is observed in the microbiota of patients with PD then, offers a plausible mechanism for increased gut-blood-brain permeability and secondary exposure of environmental and bacterial triggers thought to induce alpha-synuclein aggregation…”
- Recent work in animal models suggests that toxins produced by gut bacteria interact with alpha-synuclein causing it to behave abnormally.
- A 2017 study looked at biopsies from children with intestinal inflammation and also, at other patients who’d suffered inflammation from norovirus (a nasty gut virus) and found alpha-synuclein in the intestines that “positively correlated to the degree of inflammation of the intestinal wall.” As the first study I wrote about today suggested, this study too supports the idea that gastrointestinal inflammation and infection as potential factors in the pathogenesis of PD.” In fact, many studies now support “strong support for the theory that alpha-synuclein is involved in activating inflammation in the gut.” .
- A growing number of studies recently have suggested, in fact, that “viral particles may contribute to neurological pathology.” Remember bacteriophages? – viruses that kill bacteria? They outnumber the bacteria of our gut (which numbers in the trillions) by a factor of 10! And they “directly affect not just the populations of bacteria and fungi in the gut but the integrity of the blood-gut barrier as well.” As this article says, more studies on the potential relationships between bacteriophage infection, gut bacteria alterations and the development of PD is a crucial area of study for the future. I wrote about this in the past, here
- “With emerging studies showing an association between PD and the abundance of certain gut microbiota…cultivating healthy gut microbiota with bacteria like Prevotellaceae (a family found to be depleted in the microbiota of patients Autism-Spectrum Disorder and PD believed to maintain healthy gut and blood-brain barriers) and closely monitoring levels of Enterobacteriaceae…may represent novel ways of promoting brain health.” The article goes on to say that diet may be the best way of manipulating gut bacterial species. For example, a study done on rodents, wherein the animals were given uridine (a substance that is made in the liver and helps with the formation of synaptic connections in the brain) and DHA (an omega 3 fatty acid) found that those animals given the 2 supplements had decreased motor and GI abnormalities. (I mentioned this in a post from 2017). A 2018 study found that being on a ketogenic diet (which is highly anti-inflammatory for the brain) for 16 weeks, dramatically improved brain blood flow in mice, and also increased levels in the gut of our old friend, Akkermansia, as well as Lactobacillus. It also improved the integrity of the blood-brain barrier.
We still have so much more to learn. But in looking for things you can do now, it seems that working on reducing inflammation via a healthy diet and a trial of DHA and uridine are more than supported by the current literature. The above mentioned 2017 paper on mice and diet concluded: “This is the first study demonstrating beneficial effects of specific dietary interventions, given after full development of symptoms, on a broad spectrum of motor and non-motor symptoms in a mouse model for PD.”[iii] They gave the mice uridine, DHA and prebiotics: not exactly arduous…and it seems to me, absolutely worth a try.
[ii] Fitzgerald, E, Murphy, S, Martinson, HA. Alpha-synuclein pathology and the role of the microbiota in Parkinson’s Disease. Frontiers in Neuroscience. 2019. https://doi.org/10.3389/fnins.2019.00369
[iii] Perez-Pardo, P, de Jong, EM, Broersen, LM, van Wijk, N, Attali, A, Garssen, J, Kraneveld, AD. Promising effects of neurorestorative diets on motor, cognitive, and gastrointestinal dysfunction after symptoms development in a mouse model of Parkinson’s Disease. Frontiers in Aging Neuroscience. 2017. 9(57). doi: 10.3389/fnagi.2017.00057.
Category: Bacterial Microbiome, Immune System-Brain Connection, inflammationTags: Aging, bacterialmicrobiome, brain, Diet, gutbacteria, health, microbes, microbiome, Parkinson's Disease
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