Molecule produced by gut bacteria causes atherosclerosis
43 comments
·July 17, 2025nextos
The same metabolite, imidazole propionate (ImP), was already found to be associated with diabetes and heart failure. See for example this study in Nature Communications (2020): https://www.nature.com/articles/s41467-020-19589-w.
I think the value of the current study in Nature is that "ImP administration to atherosclerosis-prone mice fed with chow diet was sufficient to induce atherosclerosis without altering the lipid profile, and was linked to activation of both systemic and local innate and adaptive immunity and inflammation.", i.e. they provided evidence of causality in a mechanistic way, with an intervention.
However, the newspaper article overplayed novelty. ImP and other metabolites from gut bacteria have already been linked to atherosclerosis.
elcritch
Anyone know if there’s lab tests for ImP already? Is it a common or well known enough target?
nextos
These are typically measured using liquid chromatography coupled to tandem mass spectrometry. That also gives the opportunity to measure thousands of other metabolites, and thus get a broader picture of health. Unfortunately, commercial B2C metabolomics is not there yet. It's mostly used in population genomics research.
BruceEel
"The new study shows that blood levels of imidazole propionate
are lower in people with diets rich in vegetables, fruits, whole grains, fish,
tea, and low-fat dairy products."
FollowingTheDao
Not really because this might raise the chances of certain cancer in certain people.
Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1 https://pubmed.ncbi.nlm.nih.gov/39819421/
You really need to know your genetics to be certain, and make sure you have enough B6.
Meat is very high in histidine so that is why this meat, without enough B6, will raise the risk of heart disease and T2D as well as colon cancer.
null
pretzellogician
"another shocking finding: atherosclerosis was ubiquitous"... yikes, can't wait till this inhibitor makes it to market.
Anyway, fascinating. As time goes on, more "lifestyle diseases" will be root-caused like this, rather than just being due to "personal choice" and "willpower". There are a ton of them: https://en.wikipedia.org/wiki/Lifestyle_disease
1. Ulcers: (stress?)... now root-caused to H.pylori infection.
2. Atherosclerosis (Bad diet? Lack of exercise?)... now maybe root-caused.
3. ?
Yes, sure, lifestyle has something to do with any or all of these. But how much seems debatable.
Aurornis
> As time goes on, more "lifestyle diseases" will be root-caused like this, rather than just being due to "personal choice" and "willpower".
The article directly says that diet and lifestyle factors are associated with levels of imidazole propionate
> When Fuster presented the project in 2010, he noted how difficult it is to diagnose cardiovascular problems early and how simple it is to prevent them, with measures such as exercising, following a healthy diet, and not smoking. The new study shows that blood levels of imidazole propionate are lower in people with diets rich in vegetables, fruits, whole grains, fish, tea, and low-fat dairy products.
It's easy to be lured into the idea that diseases are inflicted upon us by nature at random rather than the result of our lifestyle, but in cases like this it's lifestyle and diet that shape the activity of the bacteria.
> Ulcers: (stress?)... now root-caused to H.pylori infection.
This is also a misunderstanding of the research. About half of ulcers are caused by NSAID overuse. NSAID overuse is associated with stress, too. Even without NSAIDs, stress is associated with increased stomach acid production, which amplifies susceptibility to ulcers.
So it's not correct to wave it all away and say that it's all random bacterial infections. NSAIDs are a common source, and stress can amplify susceptibility to ulcers from either cause.
pretzellogician
>So it's not correct to wave it all away and say that it's all random bacterial infections
That is not what I said (per my comment "Yes, sure, lifestyle has something to do with any or all of these.") But it seems likely we'll find that lifestyle and diet are not the only cause, maybe not even the primary one.
>>> When Fuster presented the project in 2010, he noted how difficult it is to diagnose cardiovascular problems early and how simple it is to prevent them, with measures such as exercising, following a healthy diet, and not smoking. The new study shows that blood levels of imidazole propionate are lower in people with diets rich in vegetables, fruits, whole grains, fish, tea, and low-fat dairy products.
So... cardiovascular problems can be "prevented" with those simple measures? It seems likely there are some non-smoking marathoner vegans that have died of heart attacks. But maybe he was mis-translated.
>About half of ulcers are caused by NSAID overuse.
(From https://pmc.ncbi.nlm.nih.gov/articles/PMC8002800/: "NSAIDs are second to Helicobacter pylori infection in causing peptic ulceration in the upper GI tract.")
I didn't know that! Thank you, that is very interesting.
ifwinterco
Vegan diets are associated with higher risk of stroke, so you might not get a heart attack, but it's not as simple as 'less meat and more cardiovascular exercise == good'
slibhb
> That is not what I said (per my comment "Yes, sure, lifestyle has something to do with any or all of these.") But it seems likely we'll find that lifestyle and diet are not the only cause, maybe not even the primary one.
What would it even mean for lifestyle choices to directly cause some condition?
Attributing causation is largely subjective (up to a point). It's like saying "flipping the light switch didn't turn off the lights, rather it was the cessation of the flow of electrons".
> So... cardiovascular problems can be "prevented" with those simple measures? It seems likely there are some non-smoking marathoner vegans that have died of heart attacks. But maybe he was mis-translated.
Eating right, not getting fat, and exercising dramatically lowers the risk of heart disease. Some people who do all that will still get heart disease due to some congenital condition. But the vast majority of heart disease can be avoided.
FollowingTheDao
Be sure you want to inhibit Imidazole propionate before you do so. It is know to inhibit prostate cancer. And here is a littel secret, it is kind of spoken about quietly that most people who have family history of heart disease have lower rates of cancer and visa versa.
Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1 https://molmed.biomedcentral.com/articles/10.1186/s10020-025...
https://www.nature.com/articles/s41598-024-78787-4 There exists a statistically substantial inverse association between angina pectoris and lung cancer (β = − 0.118, p = 0.001), breast cancer (β = − 0.049, p = 0.029), and colorectal cancers (β = − 0.152, p = 0.003). A noteworthy inverse correlation was observed between heart attack and lung cancer
Also Imidazole propionate is metabolized by bacteria from histidine. And Histidine turns into Histamine withe the help of B6 via Histidine decarboxylase.
So maybe people with heart disease need B6?
Vitamin B6 and cardiovascular disease https://pubmed.ncbi.nlm.nih.gov/22116704/
So it is personal choice, but you have to know the choices. Many things deplete B6, alcohol being one opf them.
tmaly
I wonder how much of our diet contributes to these gut microbes?
Aurornis
Massively. Changing diet is about the only realistic way to elicit long-term changes in the microbiome. Even taking probiotics doesn't last very long.
There's a lot of questionable microbiome science that hasn't been replicated. You can find a lot of studies that say something changes the microbiome, but it's almost always a single short-term observational study on a small group of people.
Realistically, increasing vegetable intake and reducing processed food intake are the easiest knobs you can turn to adjust the microbiome. A lot of people reach for supplements or imagine extreme measures like fecal transplants, but the practical solution is to simply buy some snacking vegetables every time you go to the store and eat them throughout the day.
TuringTourist
What is your definition of processed food? Are potatoes processed because they are cleaned? Is chicken breast processed because the chicken is plucked? Is vinegar processed because it has undergone a chemical transformation via fermentation? Are potato chips processed because they are sliced potatoes fried in oil? Are fried plantains processed because they are sliced plantains fried in oil?
I do not mean to come across as antagonistic, I just haven't been able to find a line that everyone agrees with and felt it was useful to demonstrate that by asking a bunch of questions.
healthless
> What is your definition of processed food? Are potatoes processed because they are cleaned? Is chicken breast processed because the chicken is plucked? Is vinegar processed because it has undergone a chemical transformation via fermentation? Are potato chips processed because they are sliced potatoes fried in oil? Are fried plantains processed because they are sliced plantains fried in oil?
In practice, for the vast majority, it doesn't matter where the line is drawn.
Simply moving your diet as close as possible to unprocessed food (read: minimal steps between organism and ingestion) is the goal.
Diti
My personal definition is that if you can stack the food you buy, it has been processed. It’s a subjective definition, and there might be dozens of counterexamples, but it feels true to me.
cyberax
I've heard the theory that it's the ease of separating the food into small chunks with high surface area that matters.
Most processed food is made of ground meat and various types of mush/pastes, so it easily falls apart in the gut.
adammarples
Nobody seems to agree, but the best I've been able to find is that every step counts and the level of invasiveness does too. So a plucked chicken is one thing, but a plucked, chlorine rinsed, freeze dried, ground up, centrifuged, glued, rehydrated, salted, etc. is another
mtalantikite
My immediate thought was "well, what do these bacteria feed on?".
DebtDeflation
A quick Google search reveals these bacteria produce the imidazole propionate from histidine. Unfortunately, histidine is an essential amino acid (necessary for life and our bodies can't produce it so we need it in our diet).
Aurornis
The bacteria in your microbiome aren't a fixed quantity. Changing diet will change the microbiome over time.
The researchers found that healthier diets and lifestyle were associated with lower levels of imidazole propionate. Trying to starve the bacteria of precursors isn't practical.
elektor
"A team of Spanish scientists made a striking announcement 15 years ago: they were seeking thousands of volunteers among the employees of Banco Santander in Madrid: researchers wanted to study them in depth for decades, in order to understand the onset of cardiovascular disease in healthy people."
Is there a project like this one can join in the US? I've always wanted to contribute to a biomedical study.
OleksiiA
I use this one - https://heh.eurekaplatform.org/pages/landing. I'm filling a large form every 6 months for them. Seems they focus on long term studies.
wlesieutre
"Cohort study" is the broader term for this type of work. For heart disease, the Framingham Heart Study (in Framingham MA) is a foundational one in the US.
It's not really something you can go looking to volunteer for though, someone has to be putting together a cohort study (which is a big expensive long term project) on a group that you happen to be part of, and you can agree to participate in it.
pkaye
You could look for specific studies on clinialtrials.gov. Its a database of trials in the US and also around the world. In the US I'm not sure of the status of such studies about budget cuts to NIH.
I myself was on 1 year study post organ transplant for impact of whole grain plant based diet. They educate you initially on the diet and then monitor your weight and blood tests over the year.
searine
Paid for by taxpayers via 37 academic grants and fellowships primarily from the EU. Minority contributions are from the US (NIH). One corporation (Santander Bank).
wslh
I previously posted the link to the original research here [1] but copy the link here [2] to not branch the thread.
[1] https://news.ycombinator.com/item?id=44593748
[2] "Imidazole propionate is a driver and therapeutic target in atherosclerosis" https://www.nature.com/articles/s41586-025-09263-w
epicureanideal
Atherosclerosis is, as I’ve read, a major cause of age related disease and death, so finding a cause and solution like this could be a major advancement in increasing healthspan. Another step toward longevity escape velocity.
ck2
thought that was going to be about TMAO (Trimethylamine N-Oxide)
https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.120....
https://pmc.ncbi.nlm.nih.gov/articles/PMC9235870/figure/F1/
https://pmc.ncbi.nlm.nih.gov/articles/PMC6213249/figure/nutr...
pygy_
TMAO is the precursor of imidazole propionate.
FollowingTheDao
No, it is not. imidazole propionate is made by gut bacteria metabolizing histidine.
https://www.caymanchem.com/product/33458/imidazole-propionat...
lkuty
I wonder how this study can be reconciled with the carnivorous diet, which is apparently high in good fats and good cholesterol. There is also the notion of structured water and a deficient exclusion zone which could explain the presence of plaque in the vessels according to Thomas Cowan, for example. So, I'm not sure that the factors that prevent plaque formation are those indicated. Nutrition is a complex matter.
Modified3019
“Structured water”?
I don’t know how to say this kinder than that you’ve been intellectually consuming trash, please pull yourself back.
patrickhogan1
Plaque buildup is highly heritable. So is the initial biome and often eating patterns since your parent feeds you.
snapcaster
Stop listening to cranks and grifters
meepmorp
> There is also the notion of structured water
I had to look up structured water and agree with the sibling poster: stop listening to cranks and grifters.
Great, whatever that is, and whatever that is relevant for. I fart in your direct direction, dorky.