[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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