Desulfovibrio bacteria are probable causes of Parkinson's disease: study | Hacker News Reader

Desulfovibrio bacteria are probable causes of Parkinson's disease: study

yle.fi

185 pointsatombender82 comments

Here is the paper [0] and an attempt at a summary:

A characteristic of Parkinson's disease ("PD") [1] seems to be that there are lumps [2] of a protein (alpha-synuclein, "alpha-syn" [2a]) in the neurons of patients.

What they seemed to have done is: they isolated "Desulfovibrio" bacteria strains from the feces of both Parkinson's disease patients and their healthy partners. Then they fed these bacteria to worms (nematodes [3], in particular [3a]) that were genetically modified to produce more alpha-synuclein which itself was modified to connect to green fluorescent protein (GFP [4]). They imaged the heads of the worms to detect clusters of green fluorescence.

Worms that received bacteria from PD patients showed more of these clusters than the control groups of which one was fed bacteria from healthy subjects and the other just with E.coli bacteria.

I hope I got that right.

[0] https://www.frontiersin.org/articles/10.3389/fcimb.2023.1181...

[1] https://en.wikipedia.org/wiki/Parkinson%27s_disease

[2] https://en.wikipedia.org/wiki/Lewy_body

[2a] https://en.wikipedia.org/wiki/Alpha-synuclein

[3] https://en.wikipedia.org/wiki/Nematode

[3a] https://en.wikipedia.org/wiki/Caenorhabditis_elegans

[4] https://en.wikipedia.org/wiki/Green_fluorescent_protein

It's a breakthrough but this research doesn't establish the claim in the title of the article.

The next step is to establish causality. They will have to deliberately remove (and maintain removal of) this bacteria from certain people and measure the progress of parkinsons over many years. There will also be a control group given placebos. The difference between these two groups will be the factor that crystallizes the claim made here.

It's even worse. This study was done in worms. A species of worms widely known for having literally one of the most simple neural structures of any animal on the planet (they have like 300 Neurons in total). Those worms can't even develop Parkinson's. So what they observed is that literally feeding the bacterium in large quantities to those worms coincides with buildup of a certain protein that regulates synaptic activity and whose build up is observed in a certain share of humans with Parkinson's. But the worms were also genetically modified to enhance their susceptibility towards that protein. So this result doesn't just have to jump the causality hoop, it first has to make the jump to independent confirmation. Because there is a lot of potential for unintended bias. Even if it manages that, it also has to make the jump to mammals and after that it could still fail in the clinical stage. It is at best news in a field deprived of breakthroughs for a long time, but it is far from a real breakthrough.

I only read a summary, but that is not how I interpreted the use of the worms. My understanding was that they were using the worms as a sort of biological measuring device to compare levels of that particular chemical. Is that not the case?

> It's a breakthrough but this research doesn't establish the claim in the title of the article.

What claim would that be? The only claims made in the article was that a) it's a breakthrough, and b) "Researchers say certain strains of gut bacteria are the likely cause of Parkinson's disease."

The article also refers to the bacterias as "probable causes".

Everything you pointed out supports these observations.

“Associated with” would have been a stronger claim than “probable cause of”.

"probable cause" means the same thing as "associated with", but establishes a specific hypothesis and stresses the fact that it is yet to be verified.

No. Causation is different from correlation. "Associated with" means correlation, "probable cause" means causation. Causation is the stronger statement here.

While technically association is a prerequisite for causation (correlation doesn't imply causation but causation implies correlation) probable "cause" is too strong of a term here because the experiment didn't actually do a causative test. "Possible cause" might be better here because the title heavily implies a causative study was done.

Do note that in science nothing can be proven so in actuality probable cause is really the highest form of verification that can be made. That is the claim in the title.

> “Associated with” would have been a stronger claim

in English, "stronger claim" has a meaning ambiguous between "the claim is strongly defendable, i.e. more likely to be true", and "what is being claimed is of more powerful effect". I think here the claim they are trying to point out is the powerful effect, to say "this should be pursued, its importance is elevated by its potential strong causal/explanatory effect"

This is not the team's first paper on the desulfovibrio hypothesis. Their earlier 2021 paper, "Desulfovibrio Bacteria Are Associated With Parkinson’s Disease" explains why they're looking at this:

> Conventional and quantitative real-time PCR analysis of feces from twenty PD patients and twenty healthy controls revealed that all PD patients harbored Desulfovibrio bacteria in their gut microbiota and these bacteria were present at higher levels in PD patients than in healthy controls. Additionally, the concentration of Desulfovibrio species correlated with the severity of PD. Desulfovibrio bacteria produce hydrogen sulfide and lipopolysaccharide, and several strains synthesize magnetite, all of which likely induce the oligomerization and aggregation of α-synuclein protein. The substances originating from Desulfovibrio bacteria likely take part in pathogenesis of PD.

Three of the researchers work for the Department of Microbiology at the Faculty of Agriculture and Forestry, University of Helsinki. Presumably they're interested in Parkinson's because farmers are known to have a much higher risk of PD than the general population?

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126658/

I'm from a small farming community in the Midwest. My father was farmer until my grandfather sold his farm when he was in his early 30s. My father developed Parkinson's and died from it a few years ago at the young age of 63.

The number of farmers from our community with Parkinson's is staggering.

I've been following the gut/brain theory for years. Hopefully this is going somewhere ...

> The number of farmers from our community with Parkinson's is staggering

There are many documentaries on youtube regarding pesticides and Parkinson's (France and Germany, IIRC). Some people claim that single spill on their hand gave them Parkinson, in just few years. Those pesticides are then everywhere and in everything, even if high-end wines (makes sense, wines are supposedly sprayed upto 40? times when growing).

Farming based on spraying poisons everywhere is one of the dumbest ideas of our age.

> I've been following the gut/brain theory for years. Hopefully this is going somewhere ...

Same.

The study was done on 10 patients (and their healthy spouses), which doesn't seem like a lot to make such grand claims.

One thing I don’t understand.

Don’t most people end up taking a course of antibiotics at least a few times per decade? Why doesn’t that wipe this out?

Interesting question.

The article says that there are only 8 million people with Parkinson's, so about 1 in every 1,000 person. I wonder if it is possible that only people who have never taken antibiotics after they got the disease is affected.

I’d expect docs would have tried giving these patients antibiotics though, just to see what happens. Maybe once the disease catches the bacteria can be killed off but the disease persists.

Antibiotics have major downsides. Our gut flora is quite important to our health.

A doctor worth their oath wouldn't try giving patients antibiotics "just to see what happens."

I think I was never in my life prescribed antibiotics without a warning that I have to take probiotics after each dose. Same at the pharmacy when buying prescribed antibiotics - there's always the "need probiotics as well or do you already have some?" question.

My grandfather had Parkinson's and definitely had antibiotics many times after his diagnosis, didn't help at all. After one particularly nasty infection+strong antibiotics, he got much worse overall.

I am very likely to have Parkinson's too, had antibiotics many times. Didn't change a thing about my tremor.

Even if you can good adherence to antibiotics, without specific targeting, you have always have unknown unknowns that won't be completely eradicated by a broad spectrum treatment. This study is probably finding out how to target.

Aren't gut bacteria surviving in the appendix, replenishing after antibiotics finished their course?

That is my very rough understanding. They do a number on your gut, and they probably significantly alter the balance of the microbiome, but they don't give you a clean slate by any means.

Not sure what the term of art is for the "poop pills", but feels like something like that would be required here. Maybe specially tailored to out-competing the bacteria in question.

Likely there will be bacteriophages in the environment where the Desulfovibrio arise that target it, those could make for a very specific therapy (assuming the causal link holds).

Antibiotics don't kill every microorganism. Also, our gastrointestinal tracts are repopulated from food we eat and our surroundings.

Oh, and particular antibiotics will cure a certain subset of all bacteria. So if you get pneumonia, you'll be prescribed a different antibiotic to what you'd be given if you had h. pylori. (Actually h. pylori is hard to kill, so I believe you're given 3 or 4 different antibiotics to take over several weeks)

In the gut, oftentimes antibiotics clear specific beneficial colonizing bacteria and make room for the outgrowth of pathetic ones. This is the prevailing thought as to why antibiotic use is linked to C. diff, for example.

In some countries, antibiotics are prescribed together with probiotics to ameliorate this. Shouldn't we see a reduction of PD in these countries?

(Also, did you mean "pathogenic"?)

Oh my goodness, yes, I meant pathogenic. What a silly and fitting insult.

I'm not familiar with how effective any kind of prescribed bacterial community recolonization is compared to probiotics or not doing anything.

I think the only FDA approved routes are enema and fecal transfer. I know there are capsule versions in the works, but I don't think they are FDA approved.

I expect that was meant to be "pathogenic" (unless you wanted to hurt the feelings of those rotten bacteria). And yes, it's not a complete reset, just a big reshuffle, so it's certainly a good idea to eat lots of fiber and fermented foods during and after a course of antibiotics to try and re-establish a healthier gut microbiome.

Oh my goodness, yes, I meant pathogenic. What a silly and fitting insult.

Specific bacteria is responsive to specific antibiotics. I have a family member who gets frequent urinary tract infections. They always have to characterize the bacteria to see what antibiotic it’s susceptible to, otherwise the bacteria just laughs off the antibiotic.

Antibiotics target certain bacteria and may not wipe all types even from intestines, not to mention rest of the body.

>Don’t most people end up taking a course of antibiotics at least a few times per decade?

A few times per decade sounds too frequent to me. Even once a decade sounds too frequent. I wonder where one could find stats on this.

“Researchers say certain strains of gut bacteria are the likely cause of Parkinson's disease”

This means we need to screen people then give people an antibiotic?

This is a costly disease.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240660/

“Parkinson's disease (PD) is the second most common degenerative disease of the nervous system after Alzheimer's disease”

Hopefully this turns out the same way ulcers were identified as being caused by h. pylori and not "stress".[1]

[1] https://www.discovermagazine.com/health/the-doctor-who-drank...

To provide comfy environment for h pylori development it helps to have GERD which guess what happens due to stress. So h pylori does cause ulcers, but they proliferate if you stress and in a way it's potato, potato. Choose between stress lots and take h pylori meds or, you know, not stress and be unlikely to get ulcers (and lots of other bad stuff!) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210023/

GERD - Gastroesophageal reflux disease

https://en.wikipedia.org/wiki/Gastroesophageal_reflux_diseas...

Just because A increases the possibility of B does not mean B implies that A happened. I had h pylori but no GERD (and my partner has the latter but not the former). I was completely asymptomatic.

That paper you linked to just included h pylori as a passing example of potential endogenous factors and did not make a more substantive claim. Note: I did not check any of the footnotes that mentioned H pylori, which might have done.

If you were asymptomatic, does it count as ulcers? Did you had broken stomach lining and stuff? If not, isn't it exactly what I said: h pylori does not automatically cause ulcers, unless you provide with a comfy environment to thrive by stressing/refluxing

It's more complicated:

https://nihrecord.nih.gov/2022/04/15/scientists-reveal-good-...

And I guess the story around Parkinson's (and Alzheimer's) will come out more complicated, too.

Are there any drawbacks (other than cost) to doing population wide screenings for different diseases in order to collect data and address those deseases?

The economic benefit of healthier population might actually outweigh those screening costs and accelerate medicine.

I feel like the way we’re approaching medicine testing and approval is inefficient and too complex. Many patients are resorting to social media to look for diagnosis after going to many doctors and failing to get one.

Probably you’d have a hard time getting an IRB to commit to the data collection given the kinds of real or imagined harm. We used to do this in public school. The last vestige was the scoliosis/kyphosis testing we underwent yearly in gym classes.

Seems absurdly unlikely assuming someone with Parkinson’s has taken antibiotics before. You would think this would have been noticed if so.

Wow this sounds incredible. How do people get exposed to this bacteria? Is it common enough to be a concern and how simple is the treatment?

From the paper: "DSV [=Desulfovibrio bacteria] strains isolated from PD patients and healthy individuals appear to have different traits, but it is not yet known how to differentiate between them except as presented in this study."

It seems like everyone carries these bacteria but there are more harmful strains than others (but all of them seem to faciliate the aggregation of alpha-synuclein).

If everyone has the bacteria, it’s possible as well that it’s an idiosyncratic immune thing. Much like how everyone has the same flora on their skin, yet some people’s immune system overreacts and they get Seborrheic dermatitis; most others don’t.

Strains from PD patients and healthy controls had different effects in the animal model. See my summary in a top-level comment.

So both rheumatoid arthritis and now Parkinson's disease both caused possibly by bacteria. And stomach ulcers too by H.Pylori.

Really makes you wonder about Alzheimers too.

Awesome...IF true.

And even if it merely turns out that the guilty-looking strains of Desulfovibrio bacteria are good markers for who will develop Parkinson's...that'd still be huge advance.

Warning: not published on a reputable enough journal where breakthroughs are usually published.

Front. Cell. Infect. Microbiol. IF=6.1

If you cared to look thoroughly on the metrics of the journal you would see that its a well known journal in microbiology, with a fine performance. It might be okay to dismiss a paper without reading it if its from one of the predatory publishers with +1000 journals and jpg artifacts in their page banner. But it is ridiculous to critic a pilot study with a small number of participants for not getting published in a very top journal.

Cargo culting the journal impact factor is so counter to what science is about, that its bewildering that it is so common.

Agreed. For young scientists, asking why the paper didn’t make it into a ‘better’ journal can be a good thought experiment, but dismissing it on the basis of impact factor is against the whole purpose of science.

For absolute breakthrough science that is counterintuitive in medicine, I wouldn't be surprised if it doesn't get published in top journals.

The H Pylori paper also didn't get published anywhere, no-one believed it. Nobel prize many years later.

Really interested in following this further.

Ahem, it is not a break through of Genetic Parkinson's. States that right in the 2nd paragraph.

It's somewhat comparable in factual facts manner to the Feingold book on ADHD which of course was factually, scientifically, and medically wrong from the date of its publication in the 1970s!

To me as a layman, this seems “simple” enough to have been found in the previous few decades of research. Why is it coming up only now?

The infection may not be obvious if it does not produce other visible results so it may have been considered benign by itself, the disease affects the brain but the infection is in the gut, the disease looks very much like others that are not caused by bacterial infections (instead: genetic disorders, poisoning or prions) ... so while it is indeed simple, it's rather tricky and misleading.

As a layman, I’ve always wondered why we don’t fund more medical research to cure , or treat, common diseases sooner. A lot of pain and suffering could have been avoided if we discovered a cure 20 years ago.

The investment probably doesn’t scale linearly but I imagine there’s a compounding effect.

It makes no sense that every billionaire on the planet doesn’t put 95% of their money into cancer, heart disease and neurological disease research.

They’re just waiting to die in their 60s ~ 80s from exactly the thing they could cure in their 50s.

Waiting for billionaires to solve our problems again?

The US economy is $23 trillion a year. It makes no sense that we don’t double medical research tomorrow. We’re either going to have a similar fate, or will personally know someone who will.

+1, but... 2X'ing the medical research budget tomorrow would, short-term, create zero more qualified researchers, zero more well-equipped research facilities, etc. Growing those things has a very long lead time.

But administrative bloat, salaries of upper-end administrators, etc. can be scaled up extremely fast.

Economy doesn't like past retirement people obviously.

Anecdotally, Billionaires pushing money into science so they or a loved one can live longer has been some of the most misspent research money. There have been a good number of time I’ve read about a “genius financier” or “high tech magnate” that is going to shake up drug development, but I can’t think of a win.

Michael J. Fox.

https://www.statnews.com/2023/04/12/michael-j-fox-parkinsons...

Fair and thank you I was feeling cynical this afternoon. I’ll agree his Foundation is a win. I was thinking more of companies on the focus (eg. calico) and not of funding organizations like the CF foundation (huge success story) and HHMI (great driver of scientist led science ).

The US economy doesn’t care if a billionaire suffers and dies from Alzheimer’s. But the billionaire cares. That’s why I’m surprised he spends his money on yachts and jets instead of spending 2 decades funding the world’s greatest skunkworks medical research labs.

Would megadosing (apo)lactoferrin help here? There are already nanomeds using lactoferrin for BBB transport for Parkinson's directly in the brain, how about moving it a notch down and do it directly in the gut?

This would imply that nobody ever tried to use strong antibiotics for it?

Isn't that about the simplest way to test any kind of serious disease with unknown cause?

I think that depends on the specific antibiotics used. Not all antibiotics will eliminate all bacteria.

Actually, it may be possible to argue that antibiotics make this worse if the antibiotics kill more of other competing bacteria.

There's surely some drug therapy that equates to "give them every known antibiotic, all at once, to entirely wipe out their microbiome." Presumably this is what's done before a fecal transplant, similar to how radiation is used to kill bone marrow prior to a bone marrow transplant.

(Or maybe, given that they're willing to kill everything in there, they just pump your intestines full of chlorhexidine, or some other chemical that kills like bleach but which won't get absorbed into your bloodstream?)

So how difficult would it be to selectively remove Desulfovibrio bacteria from a patient?

Antibiotics?

Probably you’d clear the gut completely with antibiotics and then repopulate it. And do the same with household family members.

Which wouldn’t be selective. Do wonder how effective this bacteria is at long term survival in a host. The source sounds specific enough (certain types of water reservoirs?). It could be beneficial to have a way to test for them - even if it’s something like a take home Covid test.

Point being I’m sure many people experience a gut level desire to avoid PD and anything like this.

Not selective, true, but we don’t have any better way to do this today.

More selective antibacterial treatments (perhaps some sort of tailored bacteriophage) would be a valuable development for many reasons, and might be just over the horizon. Unfortunately antibiotics are not especially lucrative, and the broader the spectrum (just what we don’t want) the more opportunities to get some revenue.

I suspect a breath test would be possible as is available for H Pylori.

> a gut level desire to avoid PD

Thank you for this.

There is a two-way link between gut bacteria and immunity. Immunity often forces composition of gut bacteria regardless of supplementation. Pro/pre-biotics often have no effect, we are still missing something.

"No effect" seems overly strong. From what I've read, pro/pre-biotics do help, but it's transitive and fades with time after a treatment. Troublesome, of course, as a company would much rather sell a transitive treatment than something once and done.

I’ve never understood the point of taking a probiotic unless you’d been taking antibiotics first. The various ecological niches in your gut biome would already be populated.

There is pretty minimal labeling of probiotic capsules in the grocery store (grr, Orrin Hatch) but then again nobody really knows anyway. I had my gut cleaned out due to a heavy course of antibiotics last summer and just repopulated it by kissing my partner and eating unpasteurized joghurt. Not especially scientific either, but it worked.

For example, covid wreaks havoc in the gut which might cause tilt towards bacteria producing ammonia which then leaks to blood stream, causing the brain fog. Supplementing prebiotics like lactulose can help to suppress this effect.

Before or after we'd developed a few good Desulfovibrio-targeting bacteriophages?

Stunning if we confirm this finding and manage to change the lives of people

It's quite likely that curing the infection will not necessarily help much people who are already experiencing symptoms. It may halt progression though.

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