[HN Gopher] Molecule produced by gut bacteria causes atheroscler...
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Molecule produced by gut bacteria causes atherosclerosis
Author : raphar
Score : 108 points
Date : 2025-07-17 16:21 UTC (6 hours ago)
(HTM) web link (english.elpais.com)
(TXT) w3m dump (english.elpais.com)
| tmaly wrote:
| I wonder how much of our diet contributes to these gut microbes?
| mtalantikite wrote:
| My immediate thought was "well, what do these bacteria feed
| on?".
| DebtDeflation wrote:
| 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 wrote:
| 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.
| FollowingTheDao wrote:
| > Trying to starve the bacteria of precursors isn't
| practical.
|
| Not starve them, but put them on a diet?
|
| Low B6 will lead to increased histidine by inhibiting
| Histidine decarboxylase.
|
| https://healthmatters.io/understand-blood-test-
| results/histi...
| Aurornis wrote:
| 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 wrote:
| 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 wrote:
| > 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.
| adammarples wrote:
| 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
| Diti wrote:
| 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.
| bell-cot wrote:
| So Pringles are, but regular potato chips aren't.
| cyberax wrote:
| 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.
| porridgeraisin wrote:
| I think an easy 80% solution is to have rarely stuff that
| will be called processed no matter how you draw the line
| e.g doritos
| the8472 wrote:
| https://www.frontiersin.org/journals/endocrinology/articles/...
| epicureanideal wrote:
| 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.
| searine wrote:
| 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).
| BruceEel wrote:
| "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."
|
| That's encouraging
| FollowingTheDao wrote:
| 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.
| foolswisdom wrote:
| Well, meat wasn't mentioned, unless fish counts.
| drjasonharrison wrote:
| Animal flesh wasn't explicitly mentioned, but was absent
| from the list of foods that would decrease atherosclerosis.
| tolerance wrote:
| I'll do you one better "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."
| drjasonharrison wrote:
| LOL. It's easy to recommend, or even prescribe, exercise,
| eating more fruits and vegetables, and smoking cessation. It
| is much harder to get people to change their habits and
| lifestyles.
| elektor wrote:
| "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.
| pkaye wrote:
| 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.
| wlesieutre wrote:
| "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.
|
| https://en.wikipedia.org/wiki/Framingham_Heart_Study
| OleksiiA wrote:
| 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.
| nextos wrote:
| 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 wrote:
| Anyone know if there's lab tests for ImP already? Is it a
| common or well known enough target?
| nextos wrote:
| 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.
| drjasonharrison wrote:
| Another paper describes how imidazole propionate serum levels
| were measured:
| https://www.nature.com/articles/s41467-020-19589-w
|
| """Imidazole propionate serum measurements
|
| ImP was quantified using ultra-performance liquid
| chromatography coupled to tandem mass spectrometry according
| to previous work. Briefly, serum samples were extracted with
| 3 volumes of ice-cold acetonitrile containing internal
| standards (13C3-labeled ImP and urocanate). After
| derivatization to butyl esters using 5% hydrochloric acid in
| butanol, the samples were separated on a C18 column using a
| gradient consisting of water and acetonitrile. Quantification
| was made using an external calibration curve16."""
|
| So yes, but no.
| lkuty wrote:
| 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.
| snapcaster wrote:
| Stop listening to cranks and grifters
| meepmorp wrote:
| > 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.
| patrickhogan1 wrote:
| Plaque buildup is highly heritable. So is the initial biome and
| often eating patterns since your parent feeds you.
| Modified3019 wrote:
| "Structured water"?
|
| I don't know how to say this kinder than that you've been
| intellectually consuming trash, please pull yourself back.
| NotGMan wrote:
| You could've at least googled it.
|
| Structured water is a real thing, not some hocus pocus.
|
| It's in your blood vessels for example, it forms a thin layer
| at the edges.
| pretzellogician wrote:
| "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 wrote:
| > 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 wrote:
| >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.
| slibhb wrote:
| > 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.
| pretzellogician wrote:
| Yep, totally agree with your points.
|
| >What would it even mean for lifestyle choices to
| _directly_ cause some condition?
|
| The glib answer would be something like woodworking and
| missing fingers :-)
|
| But there are plenty of people (not me!) who believe, for
| example, that obesity and type-2 diabetes are directly
| caused by overeating and/or lack of exercise.
| FollowingTheDao wrote:
| I follow the same logic you do, even though I disagree
| with what you are saying.
|
| Lifestyle choices _increase the risk_ of these diseases
| but if they _caused_ the disease, everyone who ate the
| diet would get the disease, and we know that is not true.
|
| The difference is crucial because we know genetics plays
| a role as well so matching diet and genetics would be
| useful.
| pretzellogician wrote:
| Perhaps I'm mis-stating something then, because I agree
| with you. (Just clarified my post in case that was the
| issue.)
| ifwinterco wrote:
| 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'
| FollowingTheDao wrote:
| 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 (b = - 0.118, p = 0.001), breast
| cancer (b = - 0.049, p = 0.029), and colorectal cancers (b = -
| 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.
| ck2 wrote:
| 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_ wrote:
| TMAO is the precursor of imidazole propionate.
| FollowingTheDao wrote:
| No, it is not. imidazole propionate is made by gut bacteria
| metabolizing histidine.
|
| https://www.caymanchem.com/product/33458/imidazole-
| propionat...
| wslh wrote:
| 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
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