Parkinson Disease May Start In The Gut

haidut · Oct 15, 2014

Very much in line with Peat's teachings that fixing gut health is the key to improving virtually all metabolic conditions mediated through endotoxin, NO, food toxins, etc.

http://www.lunduniversity.lu.se/article ... rengthened
http://link.springer.com/article/10.100 ... 014-1343-6

aguilaroja · Oct 15, 2014

haidut said:
...
http://www.lunduniversity.lu.se/article ... ngthened...

The abstract seems to suggest that what was shown that an injected toxin was transported "retrograde" from gut to brainstem via the vagus nerve:
http://www.ncbi.nlm.nih.gov/pubmed/25296989
"Braak and coworkers hypothesized that Lewy pathology primes in the enteric nervous system and spreads to the brain, suggesting an active retrograde transport of α-synuclein (the key protein component in Lewy bodies), via the vagal nerve."...α-synuclein present in the human PD brain lysate and distinct recombinant α-synuclein forms are transported via the vagal nerve and reach the dorsal motor nucleus of the vagus in the brainstem in a time-dependent manner after injection into the intestinal wall."

narouz · Oct 15, 2014

Very interesting, haidut!
I hope not too much of divergence,
but you have mentioned fixing a gut issue yourself,
and for one thing you noted the use of cyproheptadine.

Beyond that, how did you address your ailing gut?

haidut · Oct 16, 2014

narouz said:
Very interesting, haidut!
I hope not too much of divergence,
but you have mentioned fixing a gut issue yourself,
and for one thing you noted the use of cyproheptadine.

Beyond that, how did you address your ailing gut?

I would not say I have fixed it completely. Maybe I am at 85% the gut healthiness I had in my 20s. The carrot salad and taking digestive enzymes 3 times day seem to have placated my stomach mos of the time. At least I can sleep better. I also avoid eating more than 30g of fat with each meal.
So, it's still work in progress but my gut certainly improved over the last 6 months.

Zpol · Dec 21, 2017

@haidut @aguilaroja @NathanK @Soren

Hey all, I realize this is a very old thread but I'm wondering if one of you has any information regarding healing the gut to halt/prevent PD. This article has me very confused..

The rogue protein behind Parkinson’s disease may also protect your gut
By Meredith WadmanJun. 27, 2017 , 4:30 PM

The hallmark brain damage in Parkinson’s disease is thought to be the work of a misfolded, rogue protein that spreads from brain cell to brain cell like an infection. Now, researchers have found that the normal form of the protein—α-synuclein (αS)—may actually defend the intestines against invaders by marshaling key immune cells. But chronic intestinal infections could ultimately cause Parkinson’s, the scientists suggest, if αS migrates from overloaded nerves in the gut wall to the brain.

“The gut-brain immune axis seems to be on a cusp of an explosion of new insights, and this work offers an exceptionally exciting new hypothesis,” says Charles Bevins, an expert in intestinal immunity at the University of California, Davis, who was not involved with the study.

The normal function of αS has long been a mystery. Though the protein is known to accumulate in toxic clumps in the brain and the nerves of the gut wall in patients with Parkinson’s disease, no one was sure what it did in healthy people. Noting that a region of the αS molecule behaves similarly to small, microbe-targeting proteins that are part of the body’s immune defenses, Michael Zasloff, an immunologist at Georgetown University Medical Center in Washington, D.C., set out to find whether αS, too, might help fend off microbial invaders.

To see whether αS was indeed playing a role in the gut’s immune defenses, Zasloff, Ethan Stolzenberg of the University of Oklahoma Health Sciences Center in Oklahoma City, and their colleagues spent 9 years collecting and analyzing biopsies of the duodenum—the first part of the intestine where nerves normally produce very little αS—from 42 children unlikely to have Parkinson’s disease. (The early stages of the disease virtually never appear until adulthood.) The children had abdominal pain, diarrhea, vomiting, and other gastrointestinal symptoms, along with gut inflammation visible under a microscope. The scientists found that the αS protein was indeed present in the nerves of the inflamed intestine—and the more intensely inflamed the tissue was, the more αS the team found.

But was the αS a cause or an effect of the inflammation? To find out, the researchers turned to biopsies from 14 children and two adults who received intestinal transplants and later developed infections with norovirus, a common gut pathogen. In most, the αS protein was abundantly evident during infection. In four of nine patients—whose intestines had been biopsied before, during, and after the infection—the αS protein appeared only during the infection, but not before. (Zasloff conjectures that the five patients who showed αS production prior to infection were making it in response to another, pre-existing viral infection.)

Next, the scientists asked whether the αS protein was acting as a magnet for inflammatory cells, which are a key part of a normal immune response. In lab dish experiments, they found that αS, whether in its normal conformation or in the misfolded aggregates found in Parkinson’s disease, powerfully attracted white blood cells that are present in both acute and chronic inflammation. They also discovered that both forms of αS activated dendritic cells, which lead to lasting immunity by presenting bits of foreign invaders to lymphocytes—the white blood cells that “remember” specific microbial intruders and respond in force to later invasions. After exposing immature dendritic cells to αS for 48 hours, the team discovered that the more αS, the more dendritic cells were activated. Together, the data suggest the production of αS by nerves in the gut wall is the cause—and not the effect—of tissue inflammation, the authors write today in the Journal of Innate Immunity. “This discovery shows us that the [gut’s] nervous system can play a key role in both health and disease,” Zasloff says.

The authors note that people with multiple copies of the gene that directs the production of αS inevitably develop Parkinson’s disease—in essence, production of the protein overwhelms the body’s ability to clear it, and it forms the toxic aggregates that cause Parkinson’s. They also write that repeated acute or chronic gut infections could produce “a comparable increase” in αS.

The paper’s findings are “thrilling,” says Aletta Kraneveld, an immunopharmacologist who studies the gut-brain axis at the University of Utrecht in the Netherlands. “This is the first [study] showing that a protein very, very relevant for Parkinson’s disease is able to induce an immune response. It opens up so many avenues for new research.”

Zasloff himself is moving into the clinic, treating Parkinson’s patients for constipation using a synthetic version of squalamine, a natural steroid made by the dogfish shark. Squalamine, says Zasloff, prompts bowel movement and blocks αS action in gut wall nerves. The early phase trial is being conducted by Enterin, a Philadelphia, Pennsylvania–based firm Zasloff founded with his co-author, neurologist Denise Barbut, now Enterin’s chief medical officer. If the drug succeeds in reversing constipation, the researchers will conclude that it has disrupted the function of αS in the intestinal nerves. “This type of approach could also in principle alter the whole natural history of the disease,” Zasloff says.

But David Beckham, a neurovirologist and physician at the University of Denver, is cautious. “Potentially αS is playing some role in helping neurons fight off infections,” he says. But he adds that the current study doesn’t do enough to show that it is a cause and not an effect of inflammation.

“This is an early part of a new emerging understanding of what this molecule potentially does,” Beckham says. “And I think it’s eventually going to lead us in the correct direction as to what’s going wrong in Parkinson’s disease—and potentially to how can we prevent it.”

Squalamine is the supplement/medication they are using to reduce the α-synuclein. As indicated in this article, the gut inflammation from infection is increasing the α-synuclein, and reducing α-synuclein may prevent PD from developing after the α-synuclein crosses the blood-brain barrier, yet there is conjecture that the excess α-synuclein is there for a reason and possibly fighting off some other infection.

I don't know much about α-synuclein. I will research this more in depth. The reason I came across this is because is because the Squalamine theoretically helps with constipation, which I have chronically, also I have permeable gut (celiac and other AI disease), so I want to find a way to prevent the food proteins leaking out of my guts from getting into my brain. Also, the squalamine is one of the few substances that can penetrate the cell wall of methanogenic archaea which are the cause (or the result of) constipation in SIBO-C (which I also have). I want to take the Squalamine but obviously don't want to reduce resistance to other viruses, nor do I want to reduce the methanogenic archaea so much that I can no longer digest phosphatidylcholine and get fish smell. Seriously in a quandary.

This article was published about 6 months ago. Can anyone help find more data on this? (I know some of you may have access to medical databases that I do not)

THanks!!!

aguilaroja · Dec 22, 2017

I am not aware of newer research yet about squalamine and the aminosterols for this topic than the Perni/Zasloff paper.

There have been some studies associating gut microbiota to Parkinson’s and neurodegenerative diseases. Perhaps someone will look at them more fully through a Peat-ian lens.

NAD/NADH Ratio - The One Metabolic Cause To Rule Them All

Niacinamide And Doxycycline May Treat Alzheimer Disease (AD)

Nicotinamide adenine dinucleotide and its related precursors for the treatment of Alzheimer's disease. - PubMed - NCBI
“Increased oxidative stress has been shown to impair normal cellular bioenergetics and enhance the depletion of the essential nucleotides NAD+ and ATP. NAD+ and its precursors have been shown to improve cellular homoeostasis based on association with dietary requirements, and treatment and management of several inflammatory and metabolic diseases in vivo. Cellular NAD+ pools have been shown to be reduced in the ageing brain, and treatment with NAD+ precursors has been hypothesized to restore these levels and attenuate disruption in cellular bioenergetics.”

Progression of Parkinson's disease is associated with gut dysbiosis: Two-year follow-up study

Microbiota-Brain-Gut Axis and Neurodegenerative Diseases. - PubMed - NCBI

Vitamin D in the prevention, prediction and treatment of neurodegenerative and neuroinflammatory diseases
“In a 29-year longitudinal study involving 3173 men and women between the ages of 50 to 79 years from Finland who were free from PD at baseline, individuals with high serum vitamin D levels (> 20 ng/ml or at least 50 nmol/l) had 65% reduced risk of PD compared to those with low serum vitamin D levels (< 8 ng/ml or 25 nmol/l) [6]. Moreover, some of the clinical presentations of PD such as falls, fractures, and balance problems have been attributed to low levels of circulating vitamin D [17, 148, 153].
“The link between vitamin D and PD worsening could be explained by the fact that VDRs are highly expressed in the substantia nigra [7], a key anatomical region involved in PD pathogenesis.”

sladerunner69 · Dec 22, 2017

Why is it that my gut feels more easily irritated than before peating? My friends and family can surely eat starchy bread and pasta's and foods fried in vegetable oil like fries and chicken tenders, without complaining or being burdenned by stomach discomfort. Howevver, I can no longer even eat a sandwhich or any amount of starch without feeling an ache in my gut. I suppose there is a certain amount of conditionning occuring, and that gluten grains will be more likely to cause issues than anything.

Zpol · Dec 22, 2017

aguilaroja said:
I am not aware of newer research yet about squalamine and the aminosterols for this topic than the Perni/Zasloff paper.

There have been some studies associating gut microbiota to Parkinson’s and neurodegenerative diseases. Perhaps someone will look at them more fully through a Peat-ian lens.

NAD/NADH Ratio - The One Metabolic Cause To Rule Them All

Niacinamide And Doxycycline May Treat Alzheimer Disease (AD)

Nicotinamide adenine dinucleotide and its related precursors for the treatment of Alzheimer's disease. - PubMed - NCBI
“Increased oxidative stress has been shown to impair normal cellular bioenergetics and enhance the depletion of the essential nucleotides NAD+ and ATP. NAD+ and its precursors have been shown to improve cellular homoeostasis based on association with dietary requirements, and treatment and management of several inflammatory and metabolic diseases in vivo. Cellular NAD+ pools have been shown to be reduced in the ageing brain, and treatment with NAD+ precursors has been hypothesized to restore these levels and attenuate disruption in cellular bioenergetics.”

Progression of Parkinson's disease is associated with gut dysbiosis: Two-year follow-up study

Microbiota-Brain-Gut Axis and Neurodegenerative Diseases. - PubMed - NCBI

Vitamin D in the prevention, prediction and treatment of neurodegenerative and neuroinflammatory diseases
“In a 29-year longitudinal study involving 3173 men and women between the ages of 50 to 79 years from Finland who were free from PD at baseline, individuals with high serum vitamin D levels (> 20 ng/ml or at least 50 nmol/l) had 65% reduced risk of PD compared to those with low serum vitamin D levels (< 8 ng/ml or 25 nmol/l) [6]. Moreover, some of the clinical presentations of PD such as falls, fractures, and balance problems have been attributed to low levels of circulating vitamin D [17, 148, 153].
“The link between vitamin D and PD worsening could be explained by the fact that VDRs are highly expressed in the substantia nigra [7], a key anatomical region involved in PD pathogenesis.”

Good stuff thanks! I'm going to take some time to read through all this and fully grasp it all. There's also the issue of different factors as the cause almost like the whole thing is a different disease but with the same symptoms. I've got keep this in mind when researching.

The idea of Parkinson’s disease propagating from gut to brain has been “one of the hottest new areas of research” for several years and has become a “new mainstream,” says Patrik Brundin, an expert on Parkinson’s at the Van Andel Research Institute in Michigan. Still, the pathway is probably not relevant to all Parkinson’s patients. For instance, in some patients, alpha synuclein may begin clumping instead in the olfactory system and propagate from there to the movement centers of the brain. In other patients, autoimmune activity may play a role in neurodegeneration.

The protective role of nicotine is particularly fascinating. Red peppers can apparently suffice over taking up a cigarette smoking habit... so that's good news. It's a good think I don't have the habit already or I'd sure be seeing a reason to continue lol! (being facetious)

I am really hoping to get more info on this, like you said from a Peat-ian lense. This Zasloff is doing some amazing research. He's been shut down before due to big pharma competition. And Nu-gen, a supplier of Squalamine, has gotten sh*t from the FDA. There's something here that's big. I want to find out more in case he looses funding again or runs into FDA issues. I'm not getting my hopes up or anything. I feel myself thinking that it could be a miracle drug or something so I need to get as many other viewpoints as possible to override any dissonance brewing in my head.

Seriously thank you for these links; they will keep me busy for a while!

sladerunner69 said:
Why is it that my gut feels more easily irritated than before peating? My friends and family can surely eat starchy bread and pasta's and foods fried in vegetable oil like fries and chicken tenders, without complaining or being burdenned by stomach discomfort. Howevver, I can no longer even eat a sandwhich or any amount of starch without feeling an ache in my gut. I suppose there is a certain amount of conditionning occuring, and that gluten grains will be more likely to cause issues than anything.

From what I've researched so far there's a common sequence of events that leads to some having reactions to foods/environment and other having none to the same thing. Genetic predisposition -> a stimulus that causes a stress response, a trigger basically (trauma, or viral disease, etc.) -> a change in gene expression (SNP's) -> autoimmunity/permeable gut/inflammation happens -> now you got yourself a chronic situation. You were in the wrong place at the wrong time, the chronic illness was triggered and now it's new norm.

But yea, there's also the human factor. Our minds can be conditioned and this is every bit as real as a non-psychosomatic illness. I was very involved in hypnotherapy for a while, learned a lot. Even met a amazing lady who had her Parkinson's diagnosis "reversed" by using self-hypnosis alone (there is no 'cure' so all the doctors could say is that the dx was 'reversed'... can you even believe the absurdity). If you have an illness that is psychosomatic in nature, hypnosis (by a professional) or cognitive behavioral therapy will most likely be able to cure it. A healthy diet/lifestyle alone won't cure it.

As for gluten, there's some evidence that it's the high amount of lectins in conventional growing methods that is the 'trigger' for some, or the residual glyphosate (Round-up) which high in non-organic grains. Also, bread is not prepared in the ways it was traditionally prepared anymore, making the glutens harder to digest. Sourdough being the most traditionally prepared bread so likely easier to digest. Not for me though, I already have the Celiac.

Koveras · Feb 21, 2018

haidut said:
Very much in line with Peat's teachings that fixing gut health is the key to improving virtually all metabolic conditions mediated through endotoxin, NO, food toxins, etc.

http://www.lunduniversity.lu.se/article ... rengthened
http://link.springer.com/article/10.100 ... 014-1343-6

Oral administration of Proteus mirabilis damages dopaminergic neurons and motor functions in mice.
Sci Rep. 2018 Jan 19;8(1):1275
Authors: Choi JG, Kim N, Ju IG, Eo H, Lim SM, Jang SE, Kim DH, Oh MS

Abstract
Recently, studies on the relationship between gut dysbiosis and Parkinson's disease (PD) have increased, but whether a specific gut bacterium may cause PD remains unexplored. Here, we report, for the first time, that a specific gut bacterium directly induces PD symptoms and dopaminergic neuronal damage in the mouse brain. We found that the number of Enterobacteriaceae, particularly Proteus mirabilis, markedly and commonly increased in PD mouse models. Administration of P. mirabilis isolated from PD mice significantly induced motor deficits, selectively caused dopaminergic neuronal damage and inflammation in substantia nigra and striatum, and stimulated α-synuclein aggregation in the brain as well as in the colon. We found that lipopolysaccharides, a virulence factor of P. mirabilis, may be associated in these pathological changes via gut leakage and inflammatory actions. Our results suggest a role of P. mirabilis on PD pathogenesis in the brain.

haidut · Feb 21, 2018

Koveras said:
Oral administration of Proteus mirabilis damages dopaminergic neurons and motor functions in mice.
Sci Rep. 2018 Jan 19;8(1):1275
Authors: Choi JG, Kim N, Ju IG, Eo H, Lim SM, Jang SE, Kim DH, Oh MS

Abstract
Recently, studies on the relationship between gut dysbiosis and Parkinson's disease (PD) have increased, but whether a specific gut bacterium may cause PD remains unexplored. Here, we report, for the first time, that a specific gut bacterium directly induces PD symptoms and dopaminergic neuronal damage in the mouse brain. We found that the number of Enterobacteriaceae, particularly Proteus mirabilis, markedly and commonly increased in PD mouse models. Administration of P. mirabilis isolated from PD mice significantly induced motor deficits, selectively caused dopaminergic neuronal damage and inflammation in substantia nigra and striatum, and stimulated α-synuclein aggregation in the brain as well as in the colon. We found that lipopolysaccharides, a virulence factor of P. mirabilis, may be associated in these pathological changes via gut leakage and inflammatory actions. Our results suggest a role of P. mirabilis on PD pathogenesis in the brain.

Great find, thanks. Interestingly, this bacteria is capable of converting urea to ammonia in humans and ammonia is a known cause of PD. That study with Ceylon cinnamon for PD that I posted last year probably saw benefit due to reduced ammonia in the brain, and not just reduced NO.

Amazoniac · Feb 21, 2018

High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson's disease patients
There's a follow-up there. One of the authors is this guy.

Vitamin B2 (riboflavin) Positively Modulates The Microbiome

Travis · Feb 22, 2018

Koveras said:
Oral administration of Proteus mirabilis damages dopaminergic neurons and motor functions in mice.
Sci Rep. 2018 Jan 19;8(1):1275
Authors: Choi JG, Kim N, Ju IG, Eo H, Lim SM, Jang SE, Kim DH, Oh MS

Abstract
Recently, studies on the relationship between gut dysbiosis and Parkinson's disease (PD) have increased, but whether a specific gut bacterium may cause PD remains unexplored. Here, we report, for the first time, that a specific gut bacterium directly induces PD symptoms and dopaminergic neuronal damage in the mouse brain. We found that the number of Enterobacteriaceae, particularly Proteus mirabilis, markedly and commonly increased in PD mouse models. Administration of P. mirabilis isolated from PD mice significantly induced motor deficits, selectively caused dopaminergic neuronal damage and inflammation in substantia nigra and striatum, and stimulated α-synuclein aggregation in the brain as well as in the colon. We found that lipopolysaccharides, a virulence factor of P. mirabilis, may be associated in these pathological changes via gut leakage and inflammatory actions. Our results suggest a role of P. mirabilis on PD pathogenesis in the brain.

I thought about experimental Parkinson's a bit, and I think it's worth noting that it's always reversible. Even the classic drug used for this (MPTP) can only damage cells as its used; the rats always regain function after a few weeks.

So I adhere to metal-based theories of aluminum and iron, since these are more-or-less irreversible (takes hard work). Also, the articles by Daniel Perl and others show very strong correlations between aluminum and Parkinson's. In the 1980's: leading researcher Daniel Perl was under the impression that Alzheimer's and Parkinson's were essentially the same thing, the only practical difference between the two dependent upon what parts of the brain exactly the ingested aluminum happened to disperse.

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Parkinson Disease May Start In The Gut

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