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Endotoxin (from Low-grade Infection) As A Cause Of Crohn's, UC, And Other IBD

Discussion in 'Scientific Studies' started by haidut, Dec 21, 2017.

  1. haidut

    haidut Member

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    Not sure how many people on the forum know that Crohn's disease, which is a type of an inflammatory bowel disease (IBD), has recently been reclassified in some countries as infectious of origin and not as an autoimmune disease. The causative pathogen of Crohn's is thought to be a type of Mycobacterium
    Mycobacterium avium subspecies paratuberculosis - Wikipedia

    The change in disease type designation has only occurred in some European and Asian countries, but the FDA is also considering adding the above bacteria as a "possible cause" to its official guidelines on Crohn's. Anyways, the more important implication is that the studies which identified this bacteria as a possible cause of IBD hinted that it was not the bacteria per se which caused the damage to the colon wall but a byproduct associated with the bacteria. To my knowledge, none of the studies pointed the finger directly at endotoxin (LPS) but there aren't that many other byproducts of bacterial metabolism that can be the culprit.
    This new study points the finger directly at endotoxin (LPS) and its activity through the TLR4 receptor as a causative factor in IBD. The more important finding is that this inflammatory damage occurs as a result of recurring infections that have been resolved completely. In the actual experiment, by the fourth infection the (rodent) patients already had developed IBD and it did not resolve upon infection disappearance. Thus, treating the infections with antibiotics would likely not have much benefit. However, the study found that it was the endotoxin-driven decrease in intestinal alkaline phosphatase (IAP) which was the direct cause of intestinal damage and that raising the levels of IAP was highly therapeutic. Injections with IAP are not very practical and to my knowledge are not approved anywhere as treatment. However, one of the most potent inducers of IAP is progesterone, which Peat has actually recommended in the past to a few people with IBD. In combination with charcoal, fiber or other dietary measures that reduce endotoxin load in the colon and the blood, progesterone could be a much safer option for treating IBD than the current immunosuppressive therapies, which have a very high risk of causing cancer or a deadly infection such as PML (Progressive multifocal leukoencephalopathy - Wikipedia).


    Recurrent infection progressively disables host protection against intestinal inflammation
    "...Pathogenic infection has been implicated in the chronic inflammation seen in inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease. Yang et al. show that recurrent, low-level, and fully resolving Salmonella enterica Typhimurium (ST) infections can precipitate severe colonic inflammation in mice. ST-induced TLR4 activation resulted in increased neuraminidase 3 (Neu3) production and activity in the duodenum. This led to intestinal alkaline phosphatase (IAP) desialylation and degradation. IAP deficiency caused a marked increase in commensal bacteria-generated lipopolysaccharide-phosphate in the colon, provoking inflammation. Treatment with calf IAP or the antiviral drug zanamivir (which inhibits Neu3 activity) prevented this inflammatory cascade. This pathway may serve as an effective target for future human IBD therapies."

    Gut Reaction
    "...“We investigated whether low-titer and nonlethal salmonella infections of mice — designed to model repeated episodes of human food poisoning — might lead to cumulative and chronic intestinal inflammation,” explained Mahan, a professor in UCSB’s Department of Molecular, Cellular, and Developmental Biology. “Such a discovery might explain the origins and mechanisms responsible for human colitis and IBD.” The team experimented with a dose of salmonella that was low enough to ensure no significant symptoms or death but that allowed the pathogen to be successfully eliminated by the host. By the fourth infection — months apart from the first — the inflammation had steadily increased and colitis was now present in all subjects. Surprisingly, the disease did not improve despite the cessation of repeated infections, indicating that the damage was already done."
     
  2. pimpnamedraypeat

    pimpnamedraypeat Member

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    Amazing stuff....I've been suffering from this for years
     
  3. biggirlkisss

    biggirlkisss Member

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    how do you test for the pathogen by labs any labs out there?
     
  4. alywest

    alywest Member

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    Wow, @haidut this is incredible. Thanks for sharing your knowledge and research!
     
  5. Evgenius

    Evgenius Member

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    Here are more details on what raises and decreases IAP:
    Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet. - PubMed - NCBI
    A fat-free diet was found to have a depressive effect
    on IAP activity while fat intake stimulated IAP expression.

    Long-chain saturated triglycerides and medium-chain triglycerides increased IAP expression and/or activity,while unsaturated FAs reduced it.
    Trans FAs decreased the AP activity of intestinal brush border membranes when the amount of linoleic acid in the diet was low, whereas no effect was observed with higher amounts of dietary linoleic acid.
    Although the mechanisms linking fat absorption and IAP are beginning to be understood, nutritional studies suggest that the types of FAs and the composition of fat mixtures modulate IAP activity differentially.
    The amino acids L-cysteine and L-phenylalanine are known to be potent (I)AP inhibitors.
    IAP activity was low in rats fed a protein-free diet, and legume proteins from soybean (Glycine max) or common bean (Phaseolus vulgaris) reduced it when they were substituted for casein in the diets of rats and milk-formula-fed calves.
    Therefore, luminal deprivation or deficiency in amino acids decreases IAP, possibly via reduced intestinal epithelial growth.
    In contrast, the stimulation of IAP activity by fermented milk (yogurt) and the probiotic
    Lactobacillus casei suggests a direct effect of bacterial components or metabolites on the intestinal epithelium.
    Most simple or complex carbohydrates, including lactose, starch, cereals, and cellulose, stimulate IAP activity in the small intestine while guar gum, which is a soluble and fermentable fiber, decreases it.
    All fiber sources enhanced IAP activity in the colon, leading to the suggestion that both fermentability of and mechanical stimulation by fiber stimulate colonic epithelial proliferation and IAP activity.
     
  6. EIRE24

    EIRE24 Member

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    Would an antibiotic be the best way to clear endotoxins?
     
  7. Amazoniac

    Amazoniac Member

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    Idealabs actual probiotic. Fecal matter from burtlan as donor should be called probaeotic.
    But seriously, Koch wrote how bacterial toxins sensitize tissues to viral infection and disorganization. Perhaps it's still an infection just no longer of bacterial origin that's sustaining disorder and inflammation.

    I was dessicating my thyroid inpired by Evgenius, and the enzyme requires zinc and magnesium, both are easily lost during stress. So you're right in stating that emotional stress can be the cause of disturbances.
    Apparently it's downregulated during fasting, which can explain in part the refeeding syndrome.
     
  8. alywest

    alywest Member

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    I have been under the impression that antibiotics can clear endotoxin temporarily but only as long as the course of antibiotics lasts, then it tends to return.
     
  9. alywest

    alywest Member

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    Freakin' guar gum, man...:rightagain
     
  10. EIRE24

    EIRE24 Member

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    Guar gum causing it or to get rid of it?
     
  11. alywest

    alywest Member

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    I'm curious, have you used Activated charcoal? If so, did you ever notice a difference? ditto for progesterone...
    Check out the spoiler on Evgenius' post, it says that guar gum reduced IAP (the good stuff that fights the endotoxin), also, PUFA and soybean and legume proteins.
     
  12. EIRE24

    EIRE24 Member

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    I have tried Activated Charcoal and it has never done much for me. I am sure I suffer from SIBO and bloating and havent found much to help in the way of that
     
  13. alywest

    alywest Member

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  14. alywest

    alywest Member

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    I would also like to point out that inulin, or chicory root, is a soluble fermentable fiber (fructose oligosaccharide) that they put into a lot of probiotic and laxative supplements.
     
  15. Pointless

    Pointless Member

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    I have Crohns, and the only thing that has helped me is Cyproheptadine. And I've tried prog, dhea, preg, charcoal, R5, carrots, mushrooms, phages, tetracycline, and many other things. A lot of these make it worse. Lysine can help temporarily but with side effects.

    My metabolism is very resistant to increase. I can take 150 mcg t3 a day (do not try this) but I eventually get side effects. Anyways, lately I've normalized my body temp with high dose thiamine, about 1 g a day. This is detailed in another @haidut post that I wouldn't have known about without you so thank you.
     
  16. alywest

    alywest Member

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    interesting, does cypro keep your bowels moving regularly?
     
  17. Pointless

    Pointless Member

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    Yup
     
  18. EIRE24

    EIRE24 Member

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    What kind of improvements or dis-improvement did you get from tetracycline?
     
  19. pimpnamedraypeat

    pimpnamedraypeat Member

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    I found charcoal to be constipating and I suffer from ibs-C so constipation is a no no.

    But I did feel good and at ease from taking it. It got rid of a lot of angst and anxiety I didn't even know I had and I felt like a different person.

    TMI warming: The bathroom movement the next day was difficult and painful and put me off it
     
  20. alywest

    alywest Member

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    No such thing as TMI to a mom of two toddlers :D
     
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