9 Signs You Have a Leaky Gut

Discussion in 'Fibromyalgia Main Forum' started by ljimbo42, Feb 6, 2015.

  1. ljimbo42

    ljimbo42 Active Member


    From the reading and research I've done, leaky gut or intestinal permeability is MUCH more common than most people think. It can also be very, very difficult to reverse without a low carb. diet, antibiotic supplements, probiotics and supplements to heal the gut, if the cause is dysbiosis, which it often is. It can also be chronic use of nsaids like ibuprofen or aleve.

    For 7 years I tried using high dose probiotics (225 billion to 900 billion a day - VSL #3 ) and high dose antibiotic herbs, but that did almost nothing until I went on a low carb diet in addition to the probiotics and antibiotic herbs.

    Supplements I am having very good success with to heal the gut are aloe vera, zinc carnosine, glutamine, n-acetyl-glucosamine, DGL (deglycyrrhizinated licorice root), probiotics and inulin (a prebiotic the primarily feeds good bacteria). I take oil of orengano, and berberine to kill of the bad bacteria causing the leaky gut.

    I have completely stopped my diarrhea predominant irritable bowel syndrome that I had suffered with for over 20 years. I also just feel better in general, with increased energy and many of my symptoms of CFS that have lessened.

    My severe nasal allergies are also much improved. I am feeling improvements almost week to week now. Changes seem to be happening fairly quickly, but they never seem to happen fast enough.:) There is very little doubt in my mind now that many or most of my symptoms are caused by dysbiosis and leaky gut.
    All the best-Jim
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  2. RadioFM

    RadioFM Active Member

    Jim, sound like you have done your research based on this informative post. I also feel Diet is key to any long term gut healing strategy.
  3. IanH

    IanH Active Member

    Nice list Jim. Certainly many people with ME and FM have gut dysbiosis and this is probably related to a "leaky gut" which in turn affects symptoms.

    Many illnesses alter gut micobiota and barrier function.

    eg. fatty liver disease, the severity of disease is related to microbial imbalance but the incidence is not. The growth of gram negative escherichia spp. causes an increase in alcohol production and a worsening of the disease which is highly sensitive to alcohol in the liver.

    IBD is associated with barrier breakdown but experimentally induced breakdown does not cause IBD. It is thought that IBD severity is related to barrier breakdown and may be induced by the immune system after initiation of the disease. That is in susceptible individuals with IBD the barrier breakdown occurs and worsens the symptoms and complicates the disease.

    The primary defect leading to colitis in mice is the waning ability to clear bacteria due to an inherent defect in innate immune responses. Thus, the lack of TLR5 promotes an increase in colonic bacterial burden, and this process may enhance the activation of other proinflammatory pathways including Nfkb and a more general inflammatory state.

    Various TLR SNP's have been shown to cause IBD, ie the immune dysfunction is the trigger for the gut dysbiosis and studies of knockout TLR genes trigger animal models of IBD.

    HIV infection causes gut dysbiosis via the immune dysfunction. In HIV and the above dysfunctions the paneth cells produce Il-1 in response to the primary immune signalling. Chronic production of IL-1 in the gut causes barrier breakdown.

    Helicobacter pylori has the ability to increase the passage of food antigens across the gastric epithelium and the small intestine.

    In animal studies burn injury (and other forms of trauma) induces an increase in intestinal barrier permeability but in these cases post-injury (within 90 minutes) vagal stimulation reduces the barrier breakdown. This is thought to be by stimulation of the sympathetic nervous system which is anti-inflammatory. So the thought is that by stimulating the vagus an anti-inflammatory effect reduces the loss of barrier function. This supports the idea that barrier permeability is affected by the nervous systems.

    Chronic anxiety and severe stress causes barrier breakdown. This response appears to be mediated, at least in part, by adenylate cyclase and cAMP and links the nervous system to barrier breakdown, again via IL-1.

    Excessive intense exercise causes increased barrier permeability which in some cases is alleviated by addition of glutamine to the diet. In some people the barrier changes causes a more long term problem because of the immune system changes triggered by hyperthermia - again gut IL-1 has been implicated.

    And, then their are all the nervous system illnesses where gut dysbiosis has been shown to occur: Autism, Schizophrenia,

    Also various dietary states induce barrier breakdown.
    eg malnutrition causes bacterial imbalance followed by enteric infections. As you would expect these infections then cause immune responses and again IL-1 chronically released seems to cause barrier breakdown.

    Something, whether it be genetics or illnesses or infections alter immune function which in turn affects the microbial balance.
    This gut dysbiosis in turn causes a secondary immune dysfunction via macrophage or mast cell function leading to epithelial barrier breakdown or "leaky gut".

    Once a leaky gut condition occurs the transmigration of LPS etc. causes further immune system dysfunction in totally unrelated tissue such as the brain, this has been shown to occur in several labs.

    My position remains that in most cases of ME and FM are immune system dysfunctions which alter gut homeostasis which in turn worsens some symptoms rather than being the direct initiator of the illness. Of course we are not dealing with a single illness so it is possible that some people may have a wide-based immune system dysfunction such as ME as a result of "leaky gut" but I see no strong evidence of it - yet. However there is a strong case for improving gut function to reduce ME and FM symptoms and for most people this means using the supplements available and carefully managing diet.

    I would add the following to your list:
    vitamin D 5000iu-7000iu as this has both anti-inflammatory action as well as gram-negative bactericidal activity in small intenstine.
    glycine which is a stimulator of descending inhibitory pathway so modulating excitatory responses from NMDA and the HPA axis also impicated in neurally mediated barrier permeability.
    Last edited: Feb 6, 2015
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  4. ljimbo42

    ljimbo42 Active Member

    Ian- I agree that stressors in many forms change gut micro-biota and cause or contribute to leaky gut. In my case I think the dysbiosis and leaky gut came first, this is why this makes the most sense to me.

    I am 55 years old, and I took approximately 25-30 courses of antibiotics by my 50th birthday. Add to that a very high sugar diet up until 8 years ago (so for 47 years) and a very high stress life.

    I have also had food poisoning 2-3 or more times as well (salmonella etc.). My diet in general was high sugar, high carb. and fruits and vegetables were almost nonexistent.

    I can't imagine anyone living that kind of lifestyle for that long and taking that many courses of antibiotics and not having serious or severe dysbiosis and leaky gut, whatever the state of their immune system.

    I can't believe anyone's gut flora and gut integrity could withstand that kind of assault for so many years. It just doesn't seem possible unless you are superman and have intestines of steel-lol.

    It just seems to me, in my case, there was many stressors other than a dysfunctional immune system that brought on my cfs. It may be very possible for a dysfunctional immune system to cause cfs/fm, I truly don't know.

    I just don't think that is what happened in my case. Like you said in your post, once dybiosis and leaky gut are established, LPS (lipopolysaccharides) started leaking into my body creating a dysfunctional immune system, inflammation, high oxidative stress, impaired methylation-(which lead to higher levels of oxidative stress) and mitochondrial dysfunction.

    Many of us understand that antibiotics wipe out gut bacteria and because the healthy bacteria are usually less resistant to antibiotics. They are the first to go. Now image what 25-30 courses of antibiotics would do to one's gut flora, not counting the huge amounts of sugar I consumed! Sugar is like jet fuel for pathogenic bacteria.

    Wouldn't you agree that given this history, that it is entirely possible that my dysbiosis and leaky gut were caused by a profound assault on my gut flora and gut integrity? Too many antibiotics, huge amounts of sugar and high levels of stress,etc. over many,many years. At this point, I just can't imagine that it is not the cause.

    I am taking about 5'000 iu vitamin D a day. I am going to look into glycine in regards to neurally mediated barrier permeability, that sounds interesting. :)
    All the best-Jim
    Last edited: Feb 7, 2015
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  5. IanH

    IanH Active Member

    Jim: "Wouldn't you agree that given this history, that it is entirely possible that my dysbiosis and leaky gut were caused by a profound assault on my gut flora and gut integrity? Too many antibiotics, huge amounts of sugar and high levels of stress,etc. over many,many years. At this point, I just can't imagine that it is not the cause."

    Yes of course. Antibiotics and dysbiosis are a cause of intestinal barrier permeability.

    I am not sure about sugar (sucrose or fructose) The evidence is equivocal. If you have an increased permeability then sugars, mainly glycated proteins can cross whereas normally they cannot. Glycated (sugared) proteins can be very damaging and inflammatory. These (AGEs=advanced glycation end products and ALEs=advanced glycated lipids) are implicated in neurological dysfunction including Alzheimer's disease. Similarly I am not sure about refined carbs. While these are poor quality foods, by themselves probably do not contribute to causing leaky gut but rather contribute to the damage done after a leaky gut is established by inflammatory processes.

    The key issue is how much foods, drugs infections cause leaky gut directly or how much a changed immune system causes or exacerbates dysbiosis and int turn the leaky gut. For example there are many studies now which show that changes to inflammatory processes eg Serotonin/5-hydroxytryptamin (5-HT) produced by enterochromaffin cells in the intestine and histamine produced by mucosal mast cells acts as a proinflammatory mediators in the intestine and modulate intestinal permeability. Similarly low output of melatonin does the same.

    Here is a very good article covering the whole issue:

  6. RadioFM

    RadioFM Active Member

    "I just don't think that is what happened in my case. Like you said in your post, once dybiosis and leaky gut are established, LPS (lipopolysaccharides) started leaking into my body creating a dysfunctional immune system, inflammation, high oxidative stress, impaired methylation-(which lead to higher levels of oxidative stress) and mitochondrial dysfunction."

    I could have not describe it better my self -Keep in mind -there are many possible contributing factors at play. I have seen many people resolve there gut issues only to find out they had chronic multiple systemic infections such as chronic Lyme/co-infections diving their symptoms. These forum members spend years going to doctor to doctor with their heads cut off looking for the answers that never come.

    These lost souls come to forums like Prohealth looking for support and direction only to find a conundrum of hypothetical conspiracy theories that only drive there insecurity of no hope. Please don't miss understand the point I am trying to make as some do find supportive loving caring conversations along the way. But, many do not find the help they are looking for and go on searching with no direction. The key point I am try to make here is -we should not have to try and reinvent the wheel over and over with no clear direction of intent.

    We need a basic blue print of causative factors, testing and protocol guild lines to research.

    I like to see more threads and topics on basic lab testing, treatment option and comprehensives functional approach that have been already proven to be beneficial. We are like the blind leading the blind in a room full elephants looking for anything to quench our thirst for answers.

    The Prohealth forum needs to revision it's basic blue print and foundational supportive topics & discussion to better help it's forum members comprehend and understand these important concepts.

    We need to build a better comprehensive forum so members can research these basic topics and supportive strategies in a more organized format. We need to build and revision the basic blue print of fundamental topics.

    Prohealth Revision Topics?

    • Dysbiosis Testing -Protocol Support Forum
    • Basic Testing Support Forum
    • Lyme Testing -Protocol Support Forum
    • Mitochondria -Protocol Support Forum
    • Mold Testing -Protocol Support Forum
    • Diet/Nutritional Support Forum
    • Find A Well Informed Doctor In Your Area Forum
    • Natural Anti-inflammatory -Protocol Support

    There will always be complexes to any solution and variations to all healing strategies. The key to healing the body is understanding the contributing factors and putting the pieces back together in the right order. We need order in a sea of confusion.
    Last edited: Feb 7, 2015
  7. ljimbo42

    ljimbo42 Active Member

    Ian- In what ways do you think the immune system is changed to cause the dysbiosis and leaky gut? What do you think might have caused the changes in immune function prior to dysbiosis and leaky gut?

    I feel very strongly about the dysbiosis and leaky gut,in my case,being caused by overuse of antibiotics, stress, and huge amounts of sugar over many years,but I could be wrong. There could be other things that I am missing. I've heard having an open mind don't mean my brain will fall out-lol. Jim
  8. IanH

    IanH Active Member

    Jim: I do think that the things you mention are risk factors in developing FM and ME.

    The process which appears to be most disturbed in both ME and FM is peripheral tolerance. I am not saying that gut barrier permeability is not a factor but the evidence, in my books, say that leaky gut is a result or exacerbator of immune system changesand once started exacerbates the pro-inflammatory processes which result in symptoms.

    These reviews of evidence for leaky gut causing autoimmune disease are quite good:

    We do know that elevated LPS from commensal bacteria interfere with macrophage suppression of immune activation ie the immune reaction, whatever starts it is not switched off. Note I said commensal bacteria, it does not have to involve "bad" bacteria or gut infections, in fact under some immune dysfunction "good bacteria" can become "bad".

    Unlimited immune activation in response to signals from commensal bacteria can cause inflammation; immune responses to mucosal microbiota therefore require a precise regulatory control, it is this regulatory control which is affected.

    Interestingly there have been some studies using RNA viruses to replace commensal bacteria in mice. Such a virus is the murine norovirus which when given to gut-sterile mice serves the function of the "good" bacteria in establishing barrier function and it does it via IFN-alpha. Note that IFN-alpha is a antagonist of IL-1 receptor, and an agonist of tumor necrosis factor ( an IL-1 receptor antagonist,). (Sorry if that sounds a little complicated)

    This again lends support to the idea that the immune changes trigger increased leaky gut.

    Similarly Murine Norovirus when given to mice with antibiotic disturbed gut re-established effective gut permeability.

    While the commensal bacteria play a role in effective gut barrier they also cause exacerbation of leaky gut when the immune system is disturbed. Essentially the barrier is an interplay between the bacteria and the immune system.

    The question is: does the immune system "change" the barrier function or does it change the bacteria which then affects the barrier?

    In the animal model of MS (Experimental Autoimmune Encephalomyelitis) intestinal barrier dysfunction develops early , and can be induced by adoptive transfer of Auto-Reactive T Cells. This supports the idea that it is the Tcells themselves which create the disturbance in the gut barrier. Normal mice would not have autoreactive Tcells but when given them from another mouse the gut is disturbed because the Tregs are not developed quickly enough to suppress them.

    There is some support for the idea that a damaged intestinal barrier can prevent the body from ending an immune/inflammatory reaction in the normal manner however there is also support for the idea that ongoing or chronic stress prevents the normal cessation of the immune/inflammatory reaction. We know that chronic stress has an inflammatory effect and it also causes disinhibition. So it is possible that the chronic stress via HPA axis is increasing IL-1 in the gut which in turn triggers changes in gut permeability and there is some evidence for this.

    This can occur by sleep deprivation which flattens the circadian rhythm. People under a lot of stress can easily lose sleep for a long time. Some people have very demanding jobs or personal situations which affect sleep chronically.
    Sleep deprivation is also associated with upregulated IL-1, TNF and Nfkb and downregulation of IFN-alpha.

    In ME and FM the evidence that the symptoms are caused by disinhibition is quite strong. The role neural inhibition plays in immune modulation is little understood but it certainly does have a role. If disinhibition (loss of inhibition) occurs then immune "switch off" is affected, probably via Treg activity. This is a more plausible explanation to the elevated neurokinins such as substance P.

    It is well known that substances such as MSG and glutamates (excitatory neuro-transmitters) and aspartates in general should be avoided in FM and in ME. Conversely it is also known (somewhat) that glycine and NADH (which increases ATP) are effective inhibitory pathway neuro transmitters.


    Some people have tested high amounts of glycine with FM, with partial success. (of course such dietary tests in FM are weak due to having no biomarkers and subject to placebo).

    Excess accumulation of AGEs (advanced glycation end products, associated with cooking) is associated with FM. Ages are known to lead to stiffness, brittleness and overall alterations in tissue biomechanics of collagen rich tissues. AGES also cause constriction of micro-circulation and is also associated with increased shunting seen in FM. People with FM and consistently high AGES tend to develop spinal interdisc degeneration. It is becoming clearer that a toxic diet could predispose one to developing FM, high intakes of AGES would certainly be classed as toxic. However this is not just because of Leaky Gut.


    Whether AGES are affecting "leaky gut" is not yet known with surety (but suspected).

    Sorry its hard not to get a bit technical but I have kept it to a minimum. Hope your brain is intact.
    Last edited: Feb 10, 2015
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  9. ljimbo42

    ljimbo42 Active Member

    Ian-My brains not completely intact, but I'm a work in progress-lol. Some very interesting things there. I am going to look at the papers you posted rate now.
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  10. IanH

    IanH Active Member

    Jim: One of the supplements to not forget in the treatment of "leaky gut" is glucosamine which is used in IBD.

    Acetyl-glucosamine (GlcNAc) inhibits the production of IL-1 and IL-6. As I mentioned previously these two cytokines are detrimental to intestinal barrier function and are probably the reason why immune system changes trigger "leaky gut" in the first place. These upregulated cytokines (possibly combined with downregulation of IFN-1) appears to be the main reason for the stabilization of intestinal barrier by GlcNac.

    There are quite a few references for this in my library but I could only find this one available on the internet, there are probably more because it is a well studied supplement.


    I also know that Vets use glucosamine a lot for dogs and horses but they usually add a substance called chitosan which increases the bioavailability of glucosamine by 300%. The form used by the Vets is just the normal glucosamine HCL or sulphate because acetyl-glucosamine is more expensive.

    Both N-acetyl glucosamine and chitosan are readily available supplements.

    Another interesting but not unrelated finding is the glucosamine+chitosan when given to aging mice extends their lifespan significantly. This is thought to be due to a change in the balance between the mitochondrial ROS and the cytosolic ROS.

    Increasing mitochondrial ROS extends lifespan, however you do it, so here ROS is a good thing but increasing ROS in the cytosol decreases lifespan. What is interesting about this to me is that blankets statements about "good" and "bad" need to be taken with a pinch of salt and if you do not understand the biochemistry things can be made to sound so simple. In regard to ME/CFS and FM they are not so simple.
    Last edited: Feb 12, 2015
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  11. Alyssa-Admin

    Alyssa-Admin Active Member

    Thank you so much for providing all this very interesting information IanH. Trying to wrap my brain around it all (ok, admittedly, it is Friday afternoon, in Scotland and by 3pm my brain cells start to go on strike it seems!). I think that this topic is of interest to many. I am also curious if ProHealth might be able to do a 'pack' for repairing leaky gut. Just a thought. Have a great, pain free day.

  12. ljimbo42

    ljimbo42 Active Member

    Ian-I have been taking n-acetyl-glucosamine for 2-3 months now. I have never heard of chitosan increasing the bio-availabilty of glucosamine. You can bet I'll be looking into the chitosan to take with the NAG!

    In regards to ROS, it is my understanding, (albeit very limited) that some ROS is necessary for the body to function properly. It seems to me that the body is all about balance. Some ROS is necessary, but too much is detrimental. Some level of antioxidants are necessary, but too high a level can also cause problems.

    Something else I'll be looking into more is what you said about how NAG effects IL-1,IL-6 and INF-a. That sounds really interesting. Fascinating stuff Ian, thank you for the info!

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