Bacterial Lipids (endotoxin), Not Cholesterol, May Be A Cause Of CVD

Discussion in 'Scientific Studies' started by haidut, Nov 6, 2017.

  1. haidut

    haidut Member

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    The role of endotoxin (and TLR) in cardiovascular disease (CVD) is probably well-known by most people on this forum. Peat rarely writes on a topic without mentioning either endotoxin or keeping the gut clean as one of the main paths to good health. The role of cholesterol is finally getting to be acknowledged as at most peripheral and most likely protective instead of causative for CVD. Peat mentioned a few times that a dentists he knows stopped doing periodontal surgery after seeing that his patients got better dental (and systemic) health by simply taking laxatives. Aside from laxatives and antibiotics, I posted a few studies recently on progesterone directly opposing (and possibly reversing) periodontal disease so it should come especially handy in light of the study below.
    And if this was not enough, the bacterial lipid byproducts implicated in CVD seem to be composed primarily of PUFA, at least based on a quick search. Hopefully, somebody with access to more extensive databases can shed more light on their composition. Hey @Travis, do you have any references on the makeup of Lipid 430 and Lipid 654 mentioned in that study?

    Deposition and hydrolysis of serine dipeptide lipids of Bacteroidetes bacteria in human arteries: relationship to atherosclerosis
    "...Our results indicate that deacylation of Lipid 654 to Lipid 430 likely occurs in diseased artery walls due to phospholipase A2 enzyme activity. These results suggest that commensal Bacteriodetes bacteria of the gut and the oral cavity may contribute to the pathogenesis of TLR2-dependent atherosclerosis through serine dipeptide lipid deposition and metabolism in artery walls."

    Got a Bad Ticker? Bacterial Fats Could Be to Blame | GEN

    "...By now, most of us know that being overweight and a poor diet, often high in saturated fats, will send us down the path toward cardiovascular disease. Yet, in recent years, rising evidence has pointed to additional factors that may unduly influence the development of atherosclerosis. Case in point is the results from a new study by investigators at the University of Connecticut (UConn), which suggests that the fatty molecules clogging your arteries might come not only from what you eat but from the bacteria in your mouth. Findings from the new study were published recently in The Journal of Lipid Research in an article entitled “Deposition and Hydrolysis of Serine Dipeptide Lipids of Bacteroidetes Bacteria in Human Arteries: Relationship to Atherosclerosis.” For decades, doctors and researchers assumed that atherosclerotic lipids came from eating fatty, cholesterol-rich food. But the research hasn't borne this out—some people who consume large amounts of the foods we thought were the sources of the fat, such as eggs, butter, fatty fish, and meat, don't necessarily develop heart disease.

    "...The UConn researchers believe they may have solved part of the puzzle. Using careful chemical analysis of atheromas—the warty growth on blood vessels created by the plaques—collected from patients by a colleague at Hartford Hospital, they found lipids with a chemical signature unlike those from animals at all. Instead, these strange lipids come from a specific family of bacteria. "I always call them greasy bugs because they make so much lipid,” explained senior study investigator Frank Nichols, D.D.S., Ph.D., a UConn Health periodontist who studies the link between gum disease and atherosclerosis. “They are constantly shedding tiny blebs of lipids. Looks like bunches of grapes.”

    "...Yet despite the havoc they wreak, it's not the Bacteroidetes bacteria themselves invading. Usually, these bacteria stay happily in the mouth and gastrointestinal tract. If conditions are right, they can cause gum disease in the mouth, but not infect the blood vessels. But the lipids they produce pass easily through cell walls and into the bloodstream."
     
  2. Travis

    Travis Member

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    This sounds like it could be a lyso-sphinomyelin of sorts. The sphingomyelin phospholipid has a serine-based backbone, if I recall correctly, and I read how they used diptheria toxin to stain neurons in two separate ALS studies. I would assume that these lipids are similar and have as sphingomyelin the closest analogue to mammalian biology.

    This study gave the IUPAC name: "The (3R)- and (3S)-(15-methyl-3-((13-methyltetradecanoyl) oxy)hexadecanoyl)-glycyl-L-serine stereoisomers, abbreviated as L-serine-(R)- and -(S)-Lipid 654, were prepared according to a recent report. The details of the synthesis and verification of the enantio-enriched (R)- and (S)-Lipid 654 diastereomers can be found in (25). Details of the synthesis of diastereomeric Lipid 430 can also be found in (25)." ―Reza Nemati

    You can draw any molecule from the IUPAC name knowing the rules, but reference № 25 has a few decent line drawings: "We have also observed that lipid 430 was produced by enzymatic hydrolysis of lipid 654 and was, therefore, a logical synthetic precursor. Other fatty acids can substitute into these lipid classes, but they are less abundant relative to branched C15:0 and 3-OH iso C17:0. 6 Both of the serine dipeptide lipids, lipid 430 and lipid 654, are recovered in lipid extracts of P. gingivalis, but lipid 430 is recovered in low levels compared with lipid 654." ―Reference № 25

    lipid.png

    These are contracted by nine carbons to save space, but they inform us that they are saturated lipids by the lipid numbers "C15:0 and C17:0." It's easy to mentally extend each lipid chain, and not necessary to draw the entire chains. But you could, especially if you have ChemDoodle™ already open:

    lipid2.png Lipid 634

    And as it turns out, his naming scheme uses two carbons from the second serine's tail. This appears to be synthesized by bacteria using two separate serines for the "backbone," yet the tail for the second serine is absent. I remember seeing that sphingomyelin was made similarly in humans while investigating the βMAA explanation of ALS.

    [​IMG]

    You can see what appears to one serine minus half of the carboxylic group as the backbone, analagous to your standard phospholipid glycerol. The sphingomyelin coats the nerves, which are microtubules surrounded by pregnenolone and progesterone. Schwann cells cleave the farnesyl tail of cholesterol and deposit progensterone and pregnenolone over the nerve's inner core. There are a few associated structural proteins which are "highly" phosphorylated. It is these phosphate groups which bind the Al³⁺ atom strongly and initiate ALS.

    But all of the funding go towards explaining this away using a non-standard amino acid found in Cycad seeds called β-methylaminoalanine. There are many proposed mechanisms for how this "does it," but none actually have solid foundation in reality. The most plausible—indeed, believed by many—is that β-methylaminoalanine replaces serine in sphingomyelin. This is why you see so much research examining whether or not it can replace alanine in metabolism.

    So you might expect lipid 634 to be carried by either chylomicrons or lipoproteins in the blood and depostited on lipid membranes everywhere, including the nerve sheath—and perhaps especially the nerve sheath . . .

    The amount of this lipid could be expected to be proportional to the total amount of bacteria in the body, or perhaps even the total amount eaten. I'm not sure about the membrane compositions of all bacteria, but a few different strains make lipid 634. This could have been evolved as a toxin, a cell membrane fatty acid, or perhaps both. You might expect a bacteria with a toxic membrane to have a high chance for survival.

    This guy also measured the ability of phospholipase A₂ to cleave the lipid: "We show here that recombinant PLA₂ preparations, including human Rs PLA₂ type V and human RLp PLA₂, catalytically hydrolyze Lipid 654 to Lipid 430, despite the fact that these serine lipids are not phospholipids."―Reza Nemati

    I was just reading about phospholipase A₂. This enzyme attaches the the phospho- groups on the inner cell membrane and plucks-off arachidonic acid (or anything in the 2 position) from the glycerol backbone. It can do this to phosphatidylcholine and phosphotidylethanolamine, and is somehow "activated" by the inflammatory cytokines such as the interleukins. Some large protein growth hormones like prolactin "activate" phospholipase C to cleave innositol phosphates from the #3 position of the glycerol backbone. These insoitol phoshates chelate calcium, and are probably the key for understanding the calcium influx after prolactin activation.

    Whenever you see phospholipase A₂, you must think prostaglandins. Arachidonic acid most always exists in the #2 postition in the glycerol backbone. There are many different types of prostaglandins which can be made from arachidonic acid, and I wan't to understand what controls determines which ones exactly are produced. Some seem to be far more toxic than others, and have interesting hormonal effects.

    I think these evolved as a defense mechanism. Many protstaglandins have reactive and unstable peroxy, epoxy, and cyclo-peroxy groups.

    prostaglandin2.png

    I think these were originally made to destroy invaders, and plants do something similar. Only later had the hormonal signalling functions evolved to tell the cell's nucleus that it was under attack. I think some of them, like prostaglandin J₂, evolved to tell the cell to "just give-up already; all hope is lost. We've been attacked to such an extent that it'd be more cost-effective to just create an entirely new cell. Get caspase-3."

    Some prostaglandins seem to be intracrine hormones, but they are all involved in inflammation. But perhaps arachadonic acid can be produced in high abounts even without cell membrane disturbance (physical trauma; cytokine) by eating canola oil or something? It would be interesting to see how people or animals on a high linoleic acid diet respond to simple inflammation like burns, and I bet there are studies on this.

    So how does the cell know it's being attacked on a 0% linoleic acid diet. Do the mead acids serve as proxy for arachidonic acid?

    And do mead acids produce different, less inflammatory prostaglandins?
     
  3. Maximilian

    Maximilian New Member

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    Haidut, how do you think taking a drug like rifaximin periodically to reduce endotoxin help CVD?
     
  4. Peat Tong

    Peat Tong Member

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    How do we kill Bacteriodetes without a prescription?
     
  5. alywest

    alywest Member

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    Isn't the only real way to stop eating starches, at least for a period of time? I have tried so many routes and it seems it always comes back to the dang starches, namely grains, potatoes, rice. I'd love to bypass that and antibiotics seem to for a time, but not permanently the way starving them of fuel does.
     
  6. Dobbler

    Dobbler Member

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    According to this site Carbohydrates and Gut Pathogens safest diet when it comes to endotoxin is SCD. It allows fruits and honey but not disaccharides like lactose or sucrose. It makes sense.
     
  7. Brother John

    Brother John Member

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    Haidut you said: "...By now, most of us know that being overweight and a poor diet, often high in saturated fats, will send us down the path toward cardiovascular disease. Yet, in recent" Did you mean Saturated or Poly unsaturated?
    Thanks for posting. This is a big deal!
    Brother John
     
  8. Fractality

    Fractality Member

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    I wonder if coconut oil pulling eliminates that bacteria?
     
  9. alywest

    alywest Member

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    That was actually the quote from the article or study where they just jump straight to the idea that saturated fats are the cause of most health problems, but later they clarify that foods containing saturated fats like "eggs, butter, fatty fish, meats." Of course this is their wording. I think we are all certain that PUFAs are not good, but this article is saying that the offending fats are being produced by the bacteria themselves, and then that fat, not the bacteria itself, is being pushed into the bloodstream. Going out to get some laxatives now...
     
  10. Brother John

    Brother John Member

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    Thanks much, Brother John
     
  11. OP
    haidut

    haidut Member

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    Charcoal, alone or in combination with saturated fats, is probably a much safer GI cleaner.
     
  12. OP
    haidut

    haidut Member

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    If you combine MCT/coconut oil with insoluble fiber so that it forms an indigestible sludge, it will probably reach the gut undigested and have strong antibiotic effect there. Replacing the fiber with charcoal may do the same. The reason most people do not see quick gut cleaning effects with saturated fat is that it gets absorbed and metabollized before it reaches the colon. I think this is one reason people reported good GI effects from DeFibron - i.e. if those fats are more resistant to metabolism then they have better chance at exerting their antipathogen effects (in the gut and elsewhere).
     
  13. Wagner83

    Wagner83 Member

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    Interesting, do you notice clear effects form it or is it a preventive measure? What is your source for charcoal caps? Does it constipate you (few people have reported it did)?
     
  14. Seleniodine

    Seleniodine Member

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    Just posted this study which shows that Xylitol may be useful. Ties in to this thread as well as the benefits of the Dr Ellie oral healthcare protocol.

    Effects Of Consuming Xylitol On Gut Microbiota And Lipid Metabolism In Mice


    "Relative to mice not fed xylitol, the addition of medium-dose xylitol to a regular and HFD in experimental mice reduced the abundance of fecal Bacteroidetes phylum and the genus Barnesiella,whereas the abundance of Firmicutes phylum and the genus Prevotella was increased in mice fed an HFD with medium-dose dietary xylitol. Body composition, hepatic and serum lipid parameters, oral glucose tolerance, and luminal metabolites were unaffected by xylitol consumption. In mice, 40 and 194 mg/kg body weight/day xylitol in the diet induced gradual changes in gut microbiota but not in lipid metabolism."

     
  15. Dobbler

    Dobbler Member

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    Do you think it works other way around too and with other antimicrobial foods like raw garlic? Say you take your garlic with some MCT/CO, so it doesnt digest so fast and reaches the small intestine better? Also, which one is more antimicrobial - MCT oil or coconut oil?
     
  16. lollipop

    lollipop Guest

    Very interesting. Thank you for posting this.
     
  17. Lurker

    Lurker Member

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    Add some ACV and you have Ray’s recipe for carrot salad.
     
  18. OP
    haidut

    haidut Member

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    Lol, true. Did not think of that but it makes perfect sense.
     
  19. pimpnamedraypeat

    pimpnamedraypeat Member

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  20. Homo Consumericus

    Homo Consumericus Member

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