Parkinson's may begin in the gut, study says, adding to growing evidence | Hacker News Reader

Parkinson's may begin in the gut, study says, adding to growing evidence

washingtonpost.com

93 pointsbookofjoe74 comments

Actual paper: https://pubmed.ncbi.nlm.nih.gov/39235810/

> Conclusions and relevance: In this cohort study, a history of upper gastrointestinal MD was associated with elevated risk of developing a clinical PD diagnosis. Increased vigilance among patients with MD for future PD risk may be warranted.

Associated is the key word. The washington post sensationalizes it to "may begin in the gut"

> MD

mucosal damage

I was curious so I searched. I wonder if other conditions set up parkinsons? (Also disorders might != damage)

Causes and Diagnoses of Mucosal Disorders

The causes of mucosal disorders are generally bacteria, viruses or fungi, such as yeast. A weakened immune system, stress or dietary deficiencies can make you more prone to a mucosal disorder.

Mucosal disorders can develop in a variety of ways:

- Candidiasis is often caused by humid conditions, damaged skin or a depressed immune system.

- Canker sores are the result of a condition called aphthous stomatitis, and brought on by a weakened immune system, food allergies, viruses, bacteria and poor nutrition.

- Herpes is spread through skin-to-skin contact such as kissing and sexual intercourse. It can also be passed via a glass or lip balm of someone who has the herpes simplex virus. It can be contagious even when no lesions are present.

https://www.nm.org/conditions-and-care-areas/dermatology/muc...

The paper is about the gut-first hypothesis of Parkinson disease (PD), I don’t think the Washington Post sensationalized it that much. And the p-values they find are pretty amazing. P<.001 and still P=.01 after covariate adjustment.

It doesnt show direction of causality. Dopamine is also an important gut neurotransmitter.

and neither will the proposed treatments, and neither will the clinical trials, and neither will the approved drugs

My point is that its plausible there is no direction. It could be dopamine causing both effects.

I agree. They know dopamine makes things worse for PD pateints.

My Theory: The reason that Dopamine fails is because they do not have low dopamine, but low energy for the dopamine receptor. The dopamine receptors are G Coupled Protein receptors that need GTP to function. So if you are low in the purine GTP then it does not matter how much dopamine you make.

Giving these patients dopamine works, but then fails, because it depletes the cells of GTP.

speculative.

My work is not based on conjecture, it’s based on knowledge. So it’s not speculative, it’s a hypothesis.

This is how science works.

Sure. Interesting hypothesis. More research needed.

*edit, for the record, for me, as a postdoc, a hypothesis, while more structured than mere speculation, is still an unproven explanation that requires rigorous testing and peer review before it can be considered established scientific knowledge, and thus remains speculative.

“More research needed.”

You’re a postdoc and you don’t think this is obvious? That’s what follows a hypothesis in the scientific process.

Make an observation or ask a question.

Gather background information.

Create a hypothesis. (You are here)

Create a prediction and perform a test.

Analyze the results and draw a conclusion.

Share the conclusion or decide what question to ask next: Document the results of your experiment.

The p-values don't say anything about the size of the effect. With a large sample size, they are almost guaranteed to be small. In fact, the confidence interval after covariate adjustment comes very closing to containing the value 1, which suggests no substantive change between the groups.

That is not a sensationalization.

association indicates possibility of causation. The washington post used the right wording here.

While association does not imply causation, you very much need an association in order to establish causation. You actually need establish two associations in order to verify causation, so the existence of one type of association is already an indicator for "may begin in the gut".

You can‘t verify causation with two associations either.

Technically causation can never be verified.

But practically you need to associate cause and effect and lack of cause and lack of effect. That is two associations, and in one association the experimenter himself must deliberately influence the experiment.

This verifies cause from a practical perspective. From a technical perspective causation was not verified. Because technically you need to verify both effect and lack of effect from one population on the same event and the only way to do that is time travel.

We influenced the experiment by creating the causation but by doing that we can no longer know what would’ve happened if we didn’t create the causative precursor and thus we can never truly know if the event actually caused the effect.

Technically sometimes causation can be verified. Say you break your arm in a car crash - it's pretty clear what caused what. I'll give you that with things like gut problems and Parkinson's it's tricker.

> it's pretty clear what caused what.

It really isn't. Maybe your arm was osteoporotic or weak from a prior incident, and it broke due to a trivial pressure injury when the ambulance workers were loading you into the ambulance.

The point is that it's pretty clear only when it can be mathematically proven, and at all other times it's based on some idea of probability. In the case of this article, a causal association seems quite probable to me.

I’m of course referring to formal verification. Which means give me 100 percent concrete proof the car crash was causative. This is science and this is what all of science strives and ultimately fails to achieve.

For your example you didn’t prove anything. You gave me an arbitrary example and hoped I would understand your point through an example. I do understand your point but you failed to understand my point.

Your example is only an empathic offering of understanding but it doesn’t offer proof of your statement. Show me a formal proof of something that was causative. Anything.

You will find that on multiple levels of resolution not only can causation not be formally proven but that science can never prove anything in reality. Proof is the domain of maths and logical games of axioms and theorems we play with arbitrary rules, it does not actually apply to reality.

I mean it could be either of these three:

(1) MD induces PD

(2) PD induces MD

(3) some other underlying condition causes both MD and PD

Or (4) two unrelated things that just so happen to be coincident.

https://www.tylervigen.com/spurious-correlations

My grandfather developed both Parkinson's and Diabetes in the last ~10 years of his life. He walked regularly as a lifelong NYC resident and was not overweight. The same upper gastrointestinal mucosal damage described in this study is associated with Diabetes.

https://www.xiahepublishing.com/2472-0712/ERHM-2019-00014

https://www.gastrojournal.org/article/S0016-5085(97)00124-8/...

https://cureparkinsons.org.uk/parkinsons-and-diabetes/

Something I don't hear talked about enough is the fraction of the immune system that lives in the gut. It's something like 75% depending on what kinds of cells you include.

It seems obvious that immune related problems in the periphery would be caused by what the majority of the immune system is dealing with (which is in the gut). Immune cells have state, if they get all fired up in one place and then move somewhere else they can coordinate an inflammatory response elsewhere too. They also send chemical messages called cytokines which can circulate much more quickly and broadly, so that's another mechanism for gut inflammation to transfer to the periphery.

That's just the immune cells themselves. There's also chemicals like endotoxin that can leak through the gut barrier into circulation, the immune system creates an inflammatory response to that too, where ever it ends up. This has been called "leaky gut" and was dismissed by the medical community, despite circulating endotoxin and its origin being well understood by researchers.

I study purines and I think Parkison's and gut disorders arise with each other and neither is the root cause.

Understanding how purines (like GTP) effect neurology will lead to a more universal understanding on several neurological disorders. Low GTP leads to Parkinson's in those with other genetic risks, primarily in the Dopamine receptors.

Basically Parkinson's is a low GTP disorder.

(Just FYI, I have a purine disorder called Partial PNP Deficiency.)

https://www.sciencedirect.com/science/article/abs/pii/S03781...

https://academic.oup.com/hmg/article/26/14/2747/3768438

https://pubs.acs.org/doi/abs/10.1021/bi061960m

I wonder whether this is a side effect of degreaser, that is recognised as a cause of Parkinsons. The degreaser somehow affects the gut. That then causes Parkinsons.

[*] https://www.healthline.com/health-news/parkinsons-disease-ma...

There’s a surfactant in Roundup that’s nastier than glyphosate and may be causing a lot of problems. There a few cranks out there that have been insisting for decades that organophosphates are part of a trigger that causes Parkinson’s. I’ve always suspected they may be vindicated in the end.

They do call the gut the second brain.

I know candida in the gut has been implicated in causing symptoms like alzheimers/dementia via breaking down blood brain barrier, even leads to accumulation of plaques like in alzheimers, e.g.: https://www.medicalnewstoday.com/articles/how-a-candida-infe...

Another vector that I've encountered through personal experience with family members is mold toxins, which transit through the gut and basically keep getting recycled through the gut, so while diseases may begin in the gut, that could also just be pointing to some sort of toxic load that transits through the gut too, e.g. Ochratoxin A if it's mold exposure, etc.

Somewhere deep inside the bowels of this site there's a text file that makes things gently disappear. And I can't wait for "gut flora" to become a key value pair there.

For real. I don't get the obsession.

https://archive.is/YOGAn

> Constipation, dysphagia, older age, and higher Charlson-Deyo Comorbidity Index were also associated with higher PD risk.

doesn't parkinsons cause dysphagia? (difficulty swallowing?)

It can in advanced caseas - from my personal experience: My gran had it for as long as I could remember. As she got older and her condition worsened she would have difficulty swallowing just about anything and we had to add thickening agents (even to her water) so she could.

This also might have been a side affect of her medication but I don't recall it happening earlier on the same meds.

Take this for what it's worth. Happy to be wrong, I know someone on HN will tell me lol

Checks out for my old man, but then again his disease's progression has been so wildly aggressive - at 64 his stage of the disease is more akin to what I'd always imagined for an 84-year-old - I suspect it's not even PD

I have it in my 30s due to LPR :/. Its my life's mission atm to resolve my LPR.

Parkinson's probably has several causes, including genetic factors, but the clearest link is to exposure to environmental neurotoxins, especially organophosphate pesticides. Studies on the incidence of Parkinson's in agricultural areas where organophosphates, e.g. paraquat, maneb, were heavily used had a significantly higher risk of developing PD. The study showed a strong correlation between long-term pesticide exposure and PD onset. See:

https://www.nature.com/articles/s41467-023-38215-z

If so, what are you supposed to do about it?

Eat real food instead of the slop "food" megacorps are trying to sell you

To be honest even if there is no link that's not a bad rule to follow.

For me, I have a "nothing in a box or a bag" rule. Or more succinctly: "shop sparingly from the grocery store center." The idea is to avoid processed foods as much as possible and stick to staples, which are usually more nutritive for the dollar. Yes, rice and potatoes also come in bags, but you get the gist.

It's unfortunate so many people "fight" or argue the importance of this. Anyone, and I mean anyone, who's taken a week to eat clean, locally sourced, minimally processed food will notice a marked difference in behavior, energy level, and whole host of other benefits. It's unfortunate that access to this type of food is often limited, however, and cost or time prevents many from taking advantage of this kind of diet.

Food is such an amazing aspect to human life and I thoroughly enjoy taking full advantage of what good food can provide for my body.

Exactly.

What really gets me down is that our shopping options are often steered towards processed foods.

Take a basic cost-benefit analysis of processed foods, for example. These are an obscenely good value in terms of calories per dollar. The alternative, raw foods, take time and energy (heat/fuel) to cook before you can eat them. This puts highly processed and nutritionally poor food on the table a lot of the time if you're lacking in time, money, or both; it's the only option that makes sense in that situation. Granted, we're discounting future costs of health from a diet like this, but that's not an immediate concern when you're hungry.

It isn't always the food, we learned that from Barry Marshall

https://en.m.wikipedia.org/wiki/Barry_Marshall

Eat a balanced and varied diet with lots of vegetables/grains/fruits and make sure you get the recommended daily amount of fiber.

Depending on where you live, that comes with an assortment of chemicals, and a dearth of nutriments.

What should you eat instead in those places?

That's a good diet but maybe not protect you from Parkinson's if it really starts in the gut and is caused by e.g a virus

Everything they mentioned will benefit gut health and the immune system's ability to fight viruses.

Not true, eating more fiber can cause a bacterial overgrowth. If a particular bacteria causes PD then this would actually raise your risk of PD.

Yes, health and medicine is actually more complex than "don't eat McDonalds!"

The immune system already fight pretty well against Epstein-Barr viruses but still the infection is a a reason for developing Multiple Sclerosis.

This does nothing if the cause ends up being a bacteria, for example.

This advice is good. The broader idea that eating "healthy" solves everything is delusional.

Almost no sugar, a bit less carbs generally (but complex ones), good protein, unsaturated fat.

Or a lot of fruit & vegetables, mainly vegetables. Dinner should be smallest meal. Also limit alcohol, thats sugar in different form.

Do sports, sleep well. That's it. If it can't be tackled by decades of such approach, no point worrying but doing so will improve every aspect of your life tremendously, including happiness and life satisfaction, thats 100% guaranteed.

> Almost no sugar

I believe you meant, "Almost no added sugar," as almost all foods (vegetables and grains have some; meats/legumes generally do not) have natural sugars.

e: oops, I used an errant ' instead of "; please forgive me.

You can definitely get fatty liver by binging on fruit alone, and given that fruit juices exist and are still widely seen as a health food it's good to be specific.

It always the dosage not the source.

At least the mix from eating uncooked fruit makes it harder.

If the cause is not the diet but e.g. a virus that could be useless against Parkinson's.

But it would still make anyone's life massively better compared to not doing these, and help with tons of other potential health issues.

But OP specifically asked about Parkinson's.

Probiotics can help with gastrointestinal problems and are easy to use (they come in pills!)

As long we don't know the reason that causes the gut problems that are possibly linked to Parkinson's you can do nothing special in particular.

Could be PFAS, could be the diet, could be a virus or bacteria.

Alcohol is also pretty bad for the gut

preach. the feilds about to chase another aβ*56 dead end for a few decades.

The question is not where it begins, I have a friend who's father is diagnosed with Parkinson, can't really walk properly or talk and it's sad to see.

But what's the cure? and where's the cure. I remember that it's been questioned for so long like 5 years ago I heard that Parkinson might be a disease that begins from gut....yet we are still figuring out how it begins and not how it cures.

Is it not better to solve issues like these than AGI?

If we can prevent it, it won't be as important to be able to cure it.

Whats the prevention strategy?

As someone in their mid-30s with neurological and psychiatric conditions who also experiences regular constipation, I read this and felt, "ok, now what?"

Well, knowing something in the gut is causing it means they are one step closer to finding the cause. Eliminating the cause can prevent it, even if it doesn't aid in curing existing cases.

https://wapo.st/3XxWvVt

H Pylori, Strep, etc..

We assume that because we've named and noted the existence of these, that the limits of their bodily harm is a stomach ache, ulcers, bloating, etc...

Funny because caffeine gives me pretty bad constipation and that is always touted as a preventative, f*ck caffeine.

There's actually really strong evidence that coffee is associated with lower risk of cardiovascular disease. There's a dose-response relationship with optimal cardiovascular health at 3-5 cups per day. This is a meta-analysis that covered 1.29 million people over decades and found a statistically significant non-linear dose-response relationship. [1] This is about as good as nutrition studies get.

[1] https://pubmed.ncbi.nlm.nih.gov/24201300/

coffee != Caffeine

I cant drink coffee anymore which makes me very sad, i really like it. I causes constipation for a few days then i get unplugged in a disguting way.. it stinks and its messy.

caffeine however.. no issue. I can drink tea no issues, I can dring / consume guarana or nodoze "keep awake" tablets no issues...

for some reason after decades of drinking coffe with no ill effects I can no longer drink it specifically (decaf or not)

Combine coffee with Jack's Spicy Chicken and I have the opposite for 4 days. Hope that helps.

Majority of the immune system is in the gut. It is also one of the main culprits that Long COVID researchers are finding RNA in causing immune dysfunction.

> High uptake in the gut was observed in people with persistent post-COVID-19 symptoms, as was single and double-stranded SARS-CoV-2 RNA in gut lamina propria, as measured directly by ISH in a subset of participants

With modern day technology, we are now able to scan the whole body before and after a treatment. This can be applied to many diseases like Parkinson's, but largely being used in Long COVID trials today:

> The ability to quantify pathogen and immune responses across the whole body before and after a therapeutic intervention could provide unparalleled information on infections that primarily persist in specific tissues outside the systemic circulation

Finally, we really are entering a renaissance of being able to see our immune system in action for the first time. This will hopefully bring a cure to many diseases that are now thought to be driven by immune dysfunction / viral persistence / autoimmunity / etc.

> Nonetheless, we are just entering a renaissance of specific noninvasive nuclear imaging developments to determine immune responses to pathogens and malignancies. For these to be realized, significant resources must be provided to develop, implement and improve these emerging noninvasive technologies and facilitate their implementation into clinical trial infrastructure.

https://www.nature.com/articles/s41590-024-01948-0 (may be paywalled, but is a great article)

Beyond the nuclear imaging technologies, new tools like single-cell RNA sequencing, CRISPR screens, 5′-VDJ repertoire analysis, spatial transcriptomics, dual RNA sequencing and metagenomic sequencing, etc will help in unraveling the complexities of these complex diseases.

Bonus: Here's a video of a friend who did this experimental imaging for Long COVID:

https://www.youtube.com/watch?v=QPwXRZFhGOM

Hippocrates said all disease begins in it, so maybe we should've listened.

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