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Gut Infection Could Underlie Symptoms in Chronic Fatigue Syndrome

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Reprinted with the kind permission of Cort Johnson and Health Rising.

“We are cautiously optimistic regarding these results because, if confirmed, we may have identified a contributing factor to the innate immune issues associated with ME/CFS and a molecular target for potential treatment strategies.” – Lombardi et al.

Over the past couple of years the Whittemore-Peterson Institute has been quietly digging into the human gut.  They found that the duodenum –  the first section of the small intestine –  of  many people with ME/CFS is inflamed and has become infiltrated with lymphocytes (disease-fighting white blood cells) – a clear sign that the immune system is on the attack.

Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins. De Meirleir KL, Khaiboullina SF, Frémont M, Hulstaert J, Rizvanov AA, Palotás A, Lombardi VC. In Vivo. 2013 Mar-Apr;27(2):177-87.

Further investigations indicated that innate immune cells called plasmacytoid dendritic cells (pDCs) were present in higher than normal levels.  The first part of the immune system on the scene of a pathogen attack, the innate immune system initiates a kind of a broad inflammatory attack against pathogens. It’s the innate immune system that’s behind those flu-like symptoms you experience when you get a cold.

Dendritic Cells

Swarming the tissues in our body (skin, nose, lungs, stomach and intestines) that pathogens first come into contact with, dendritic cells (DCs) are an important part of our immune response.  If they find an invader, they snatch a piece of it (an antigen) and then dash back to the lymph nodes where they present it to T-cells for inspection.

The type of DCs the WPI found in ME/CFS patients – plasmacytoid dendritic cells (pDC’s) – are a bit different, however.  Much more than just messenger cells, pDCs are actually important virus-fighting cells that produce huge amounts of antiviral cytokines such as type-1 interferons (IFNs) when activated.  Both the pDCs and the interferon they produce activate natural killer cells – which tend to be dysfunctional in ME/CFS. Usually quite rare, they typically make up just 0.4% of the lymphocytes in the blood.

Dysregulated pDC’s dendritic cells have been associated with the some autoimmune disorders.

HERVs The WPI found higher than normal levels of pDCs in the duodenums of ME/CFS patients. When the WPI took a deeper look at the pDC’s they found them to be infected with endogenous retroviruses called human endogenous retroviruses or HERVs.

Endogenous retroviruses are ancient bits of retroviruses that have made their way into our DNA. Almost all are now benign bits of degraded DNA; a few retain enough of the original viral DNA to become partially active.  Some HERVs able to initiate destructive immune responses have been associated with autoimmune disorders such as Sjogren’s Syndrome, multiple sclerosis, and lupus.

Autoimmunity and the Gut

What do autoimmune disorders have to do with the gut? There’s a good chance the gut may play an important role in the development of some autoimmune disorders.  The idea goes something like this: first, leaky gut linings allow massive amounts of gut material to leak into the bloodstream. That gut material then triggers a a massive immune response that overwhelms the immune system’s ability to keep itself in check and it begins mistakenly attacking the body – resulting in autoimmunity.   Several studies have associated celiac disease – which can impair gut linings – with an increased risk of autoimmune disorders.

pDCs also play an important role in triggering B-cells to produce immunoglobulins to commensal (non-harmful) gut bacteria. Damaged pDC cells could result in bacterial overgrowth, intestinal dysbiosis, and other gut issues. The symptoms associated with all of these problems, of course, are common in both ME/CFS and FM.

Digging Deeper!

The WPI found pDCs with HERVs; then, in rather impressive fashion, they set out to determine why they were there.

First, they created a laboratory model of pDCs producing HERVs. When they analyzed those pDCs they found they were producing high levels of certain proteins. Then they looked to see if those proteins were present in the guts of ME/CFS patients with pDCs, and they were.

That means that HERVs they found were indeed active – a key finding.  Whether or not they’ve causing gut and other issues is another question, but the potential is definitely there for these infected pDCs to produce bacterial overgrowth (believed common in both chronic fatigue syndrome and fibromyalgia), altered bacterial flora, and other gut issues.

Obviously quite intrigued by that finding the WPI then looked to see if a genetic weakness could explain the presence of the HERVs in the ME/CFS patients. A gene polymorphism study identified a set of gene polymorphisms (alterations) more commonly found in ME/CFS patients with gastrointestinal (GI) issues.  An in-depth analysis of genes associated with the innate immune response found significant differences in these patients as well.  The findings are preliminary, but they could be describing a patient population that’s genetically at risk for innate immune system derived issues (pDCs) in the gut – and perhaps autoimmune issues as well.

They’re attempting to confirm the polymorphism findings in a larger group of ME/CFS patients as well as in an additional group of ME/CFS patients from three different continents.

Making Progress – Under the Radar

The WPI is no longer in the news much.  Instead they’re moving cautiously and methodically to explore an intriguing finding. If it all works out, they may have a molecular target they could conceivably use to shut off the HERV production and perhaps help resolve gut issues and even autoimmune tendencies and immune activation in ME/CFS.

Gut Work on the Clinical Side

“There are multiple steps in my treatment protocol that appear to be working well for a majority of my patients, but we still have much more to learn before we can successfully treat all of those who are affected,” – Dr. De Meirleir.

Dr. De Meirleir’s statement that his treatment protocols are working well for most of his patients was borne out by a recent Norwegian ME/CFS survey that identified Dr. De Meirleir as a physician with good success rates (2/3 improved; 1/10 declined).  Now, as the Medical Director of the WPI, Dr. De Meirleir may have been the first ME/CFS physician to focus heavily on the gut.

At a WPI lecture Dr. De Meirleir stated he generally begins healing the guts of his patients, a process that involves identifying dietary issues (including the removal of dairy, gluten, and fructose) and used fecal analysis to determine if a pulsed program of antibiotics, probiotics, and prebiotics and digestive enzymes will have a positive effect.

Dr. De Meirleir ended his lecture suggesting ME/CFS fits in a continuum of autoimmune diseases that includes lupus, RA, type 1 diabetes, and relapsing/remitting MS, all of which involve a dysregulation of the 2’-5’OA synthetase (RNase L pathway and Th1/Th2 immunity.

An Aside: the Gut – A Complicated Place

Since the gut with its millions of bacteria is one of the most complicated parts of the body, it’s no surprise that the treatment picture is rather complicated.

The WPI’s findings – if validated – could help simplify a complicated situation in the gut The fact that Audrey, for instance, had responded pretty well to dietary restrictions, then didn’t respond to antibiotics/probiotics, and then responded very well to fermented foods simply demonstrates how individualized gut treatment plans can be (and really, how they must be to be effective).

We saw Esther find many ME/CFS symptoms get better or resolve with Xifaxin – an antibiotic focused on the gut. We covered a study suggesting that some herbal preparations were as effective as antibiotics.  Dr. Rowe reports that ME/CFS patients with undiagnosed milk allergies will probably benefit little from other potentially beneficial treatments until milk is removed from their diet.
We’ve covered gluten-free diets, FODMAPS, and low glycemic and Mediterranean diets. We still have Paleo, anti-inflammatory diets and anti-histamine diets to go.

The gut is a complicated place – it’s going to take quite a while to fit the right combinations of probiotics, prebiotics, antibiotics, fecal transplants, herbs, foods, etc. to help a particular patient. That kind of complication makes the WPI’s gut studies all the more interesting. If infected immune cells in the gut are behind all this mess – and we’re a long way from proving that – it makes the process of fixing the problem all the simpler.

Stay tuned. The last study the WPI published was in 2013. We should know much more about how this research is stacking up this year.

Chronic Fatigue Syndrome and Fibromyalgia Microbiome – Work Under Way

Multiple rejections to Dr. Lipkin’s microbiome grant application notwithstanding, the gut in ME/CFS is getting some attention. Dr. Chia, of course, has presented his findings on enteroviral gut infections in ME/CFS. Besides his and the WPI’s work several gut studies are underway or have been completed recently. Some promising gut work is underway but needless to say much more is needed to understand the guts effects on ME/CFS and FM.

We await the publication of the Solve ME/CFS Initiative’s study of gut flora changes after exercise. Rebecca Hansen’s large Microbiome and Inflammation  (an NIH-funded study) examining bacterial composition in both the gut and blood as well as endotoxin and lactoferrin levels is due to finish up this year.

Dr. Pridgen’s antiviral study grew out of a belief that herpes virus infections in the gut play a key role in fibromyalgia. The study included a pathological screen of herpes viruses in gut tissues and will be published this year. The Lipkin/Chronic Fatigue Initiative/Microbe Discovery project is identifying viruses, bacteria, and fungi in fecal samples as well as cytokines in the blood, taken from 100 ME/CFS patients and 100 carefully matched controls.

Finally, Fluge and Mella are using endoscopy, biopsys and ultrasound to assess gut functioning in ME/CFS patients receiving Rituxiimab.


About the author: Cort Johnson has had ME/CFS for over 30 years. The founder of Phoenix Rising and Health Rising, Cort has contributed hundreds of blogs on chronic fatigue syndrome, fibromyalgia and their allied disorders over the past 10 years. Find more of Cort’s and other bloggers’ work at Health Rising.

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9 thoughts on “Gut Infection Could Underlie Symptoms in Chronic Fatigue Syndrome”

  1. BeckieC says:

    I forgot to mention a couple things that help me get through a full course of prescription antibiotics, antimicrobials, anti-fungals, recurring gut infections. The first is a recipe from researcher Garth Nicolson, PhD, a secondary victim of Gulf War Illness that he acquired from his daughter who served during 1991 Desert Storm.
    That is whole lemon-olive oil drink. Fresh-squeeze juice from one lemon with 2 tablespoons extra virgin olive oil. Add honey if necessary to swallow tart lemon juice. This recipe helps restore normal gut flora and reduces the chance of yeast infections or bacterial overgrowth from antibiotics that break down in the intestine rather than the liver. Whole lemon-olive drink is particularly helpful if you must take doxycycline, which causes major nausea and vomiting.
    Another is omega oils that reduce inflammation in the small intestine. I have taken omega oils up to 3 times per day to quiet the growling or rumbling that gut infections cause. I find a brand that includes lemon extract to prevent after-taste or nausea, dry heaves, hiccups or belching.
    Inflammation throughout the digestive tract is the first clue of infection. If you can reduce inflammation of the small intestine, you may circumvent future gut infections.
    Spicy peppers contain colchicine, a natural anti-inflammatory. I remove seeds from any kind of jalapenos and apply diced peppers to appropriate foods, such as scrambled eggs. Fresh peppers are much hotter than pickled peppers. Other less heated peppers include anchovy or poblano. Much hotter peppers include schezuan and hobanero.
    You can buy bottled hot sauce that has no preservatives rather than process peppers yourself. I found that dried peppers that I re-hydrate are helpful. I have heard testimony from a Marine Corp pilot who cured parasites he acquired while serving in a third world country by consuming many jalapenos. The parasites passed with digested peppers within 48 hours. The parasites never recurred, as they usually do in immune-compromised patients.
    Both garlic and onions are natural anti-inflamatories. So I use both either raw or while cooking. If you are not a fan, Quercitin tablets are extracted from onions and garlic and other vegetables full of anti-inflammatories.
    The best anti-inflammatory I buy is guaifenisen. The only place I can find guaifenisen is online here at Pro-Health. Guaifenisen is no longer available by prescription in its purest form. Prescription syrups do not contain enough guaifenisen to prevent me from inflammation system-wide or gut infections.
    I hope this helps you treat yourself at home.

  2. Sandy10m says:

    My initial infection with CFS started with a mono-type illness in 1984 that never went away. At exactly the same time, I became unable to eat onions (especially raw). I used to eat onions all the time, loved them, grew up on them. But onions would cause raging diarrhea within 30 minutes of eating them. Eventually I figured this out (through food elimination) and I avoid onions now. I am convinced that my intestines became infected with something in 1984, particularly at the top of the small intestine. Otherwise, how would my system react so quickly? So this article makes a lot of sense. But, what in the world is causing this? Probably a virus because I have been on a ton of antibiotics with no effect. Please work on finding the cause and cure.

    1. traceychace says:

      Hi. Is anybody able to give me an idea of the symptoms of gut infection please. I am having a lot of trouble with feeling sick & diarriea which knocks me off my feet as I feel so unwell & my Dr is a little lost as to what’s wrong. So some info would be great fully received
      Many thanks.

      1. BeckieC says:

        Where to start? My gut agony is the second predominant symptom of my disease, certainly the most debilitating, linking me to my bathroom more days than not. Obviously, chronic exhaustion was and remains primary symptom.
        First of all, stool kits that gastroenterologists preferred throughout the past 30-plus years have never revealed anything. That is partly because most parasties / amebas are dissolved by gastric acids by the time stool passes. It is also because all of my gut infections have been clear tissue. Sheets or rings of “cellophane” floating on top of the water in toilet. Or long, clear, sticky strings along all mucus membranes. The stings come through my nose, out of my sinuses and my nasopharygeal tract. Only sulfa has eradicated this particular infection of mucus membrane.
        Infection that spread from my inner ear and sinuses, imitating chronic sinus infections, down my esophogus through my digestive tract. All of my mucus membrane felt tacky or sticky, even after showering with soap.
        Secondly, those barium enemas and barium drinks for upper GI / small bowel series can make you sicker for radiation poisoning than they can possibly help – once again because sheets and rings of gastro infections are clear. I have endured a dozen CT scans of my abdomen, all to no avail, because my gut infections are consistenlty clear.
        Also, I could never provide 3 stool samples after I was vaccinated to death before Desert Storm 1990. Because everything I passed was clear liquid or undigested food.
        The most helpful prescriptions have been Qustran powder, which stops persistent diarrhea and cramps long enough to visit a doctor before diarrhea begins again. Questran is not an answer, because it holds the infections, allowing them to thrive within the Questran powder. Diarhea from accumulated infection returns after Questran passes as formed stool.
        Most helpful after that was sulfa drug to stop rumbling, ripping pains, and associated cramps. All of my small intestine feels bruised when certain infections are at their peak. I suffer no fever, but sweat profusely for all the toxins spread throughout my trunk, pressing up against my diaphragm and interfering with my heart electronics.
        Metronidazole, specifically for giardia, helped eradicate 2 more infections that were not giardia at all. Giardia thrives on the first part of the small intestine, cannot be traced through stool kits. This infection was in the last 10 feet of my small intestine, swelling and interfering with my bladder and my uterus.
        I suffered “Leaky Gut Syndrome” when my immune system became overwhelmed with infections and heavy metals detox efforts (suppositories). I developed Lactose Intolerance so that I can tolerate only yogurt and fage. 70% of the population suffers Lactose Intolerance, but doesn’t realize it because most people do not ingest major quantities of dairy, besides plain yogurt and fage. I rarely drank regular milk due to serious child abuse when I was newborn through first grade. But I ate dark cheeses and other cultured dairy products.
        I also suffer gastroperesis – small rings of infection throughout my small intestine. When food or drugs hit the ring of infection, whatever was swollowed comes back up. Gastroperesis is both paralysis and infection of small segments of the small intestine. Metronidazole beats back infection, which always returns.
        My first medical procedure (biopsies and aspirates of my duodenum) showed “chronically inflamed duodenum”, the first (10-inch) section of the small intestine right after the stomach, which is home to the bile duct and the fat enzymes duct.
        If the duodenum is inflamed or swollen, neither duct will eject necessary enzymes to break down food. A sure sign of chronic inflammation of duodenum is bowel movements of undigested food and clear water – no bile, no odor, no fats broken down. You can easily identify what you just ate about 4 hours before whenever you are suffering chronically inflamed duodenum.
        I never found any sensitivities to celiac sprue or gluten. I know that I have been infected with salmonella, cyclosporidia, giardia, Montezuma’s revenge, several other food-borne parasites, just because my immune system is chronically impaired.
        I wash all of my produce in vegetable soap. And I towel dry everything before I eat it raw, freeze it, refrigerate it, put it on the stove to cook in filtered water. Nonetheless, watery produce that has come in contact with contaminated produce still renders sickness in CFS patients. Best advice is to skip any watery produce that is shipped alongside imports. You can consume anything that is already packaged – strawberries, blueberries in plastic cartons – or any fruit that must be peeled.
        I believe that I suffer multiple gut infections, simultaneously or not – bacterial overgrowth, fungal overgrowth, pancreatitis due to Hep B vaccine, viral infections due to my chronic CMV infection, numerous bacterial infections derived from all food sources because no food is pure, not even organic.
        Growing your own is usually not an option. But beware of organic because much of the organic fertilizers cause me much gastro distress. Organic eggs frequently come from chickens that feed on sea shells. I can’t take that much mercury. And I cannot eat white cold storage eggs. I eat only “cage-free” brown eggs.
        Know that as long as you suffer diarrhea, as long as you endure cramps, lower back pain, particularly in conjunction with pain inside the rib cage, abdominal pain or chronic nausea to the point you cannot eat, you are infected by something or several things.
        My only approach for the past 24 years has been to assault the infections with whichever “cocktail” of prescription drugs diminish the symptoms. And one course of each may not be enough. It usually has not been for me, because I have been host to these infections for 24 years. I did not receive any practical medical treatment for 7 years.
        After all, my most recent bout of chronic diarrhea has lasted 9 months, that I can tell. It’s hard to tell what else you suffer, if you can confirm that you suffer Leaky Gut Syndrome and Lactose Intolerance, or any 2 chronic food-borne infections.
        You should also learn about GMOs and avoid them at all costs. I do not eat corn or anything with its byproduct High Fructose Corn Syrup. Obviously, I do not eat dairy any more. I have yet to find Lactaid products in a grocer near me. But I don’t trust any dairy or yogurt unless it is cow hormone free or “rBST free”.
        Soy is genetically modified with herbicides, and makes me deathly ill for the time it takes soy to pass through my system – 72 hours or so. Soy is in 90% of baby foods. I don’t know how our younger generations will survive cancer.
        If you can find one or 2 foods that you can tolerate while you get off the foods that make you so sick, it will be easier for you doctors to identify what type of infections you are hosting – food-borne, fungal, bad bacterial overgrowth, traveler’s diarrhea that can come back for inadequate treatment the first time.
        You should read reliable online medical websites that provide most accurate information about each of the gastro diseases. There are 100s of them. Because you suffer an immune disorder, you could be hosting 100s of gastro diseases.
        When I find an article or a medical abstract that describes my gut symptoms, I save it to pdf file or a document that I can e-mail to my doctor. Then I research prescription drugs used to treat that disease and document every section, including drug interactions and side effects. Most useful is “off-label” use of prescription drugs or alternative diagnoses to the disease the drug was initially designed to treat.
        Stay away from OTC gut remedies unless your doctor specifies. I take an incredible number of physician formulas, or supplements that practicing physicians manufacture under their own label on their medical practice websites. Lots of them are sold on ProHealth website. Be sure your doctor says OK before you take anything. Some digestive enzymes have almost killed me due to infections that thrive on them. Surprising, but believable.
        Good luck with all of this.

      2. MaureenVG says:

        I have found that Aloe AMP helps me when my gut symptoms flare up.

      3. Sandy10m says:

        Hi Beckie,
        I hope you are doing well. I am reading some old emails now and catching up. I realized that I didn’t talk about taking Viread, which is an AIDS medication that goes after the retro-virus in HIV. Because I have a high EBV load, my doctor and I decided to try it, and it has done a lot for me. Epstein Barr Virus is a retrovirus, similar to HIV in AIDS. There is nothing currently used to treat EBV. Our decision to use Viread was a difficult one, but one that I definitely am happy about. I have experienced no side effects other than positive ones, such as my migraines decreasing. It is possible that Viread could help you too. Hopefully you have insurance that covers it, since it is expensive. I am a GWS patient too. Good luck!

    2. BeckieC says:

      Most physicians describe foods passing undigested in CFS patients as “malabsorption”. I set out on a mission to find enzymes that improve absorption and cut down the number of hours I spend in the bathroom.
      I, too, developed intolerance of pickles, pickled okra, sun-dried tomatoes. Onions and garlic cause my food to pass through quicker than I would prefer. I tolerated everything I just listed before CFS / GWI.
      Now many fresh foods pass through undigested a few hours after my meal. I have conducted exhaustive research in my effort to “dry up” my aching gut, watery stools, persistent diarrhea that can last for 13 hours.
      When researching supplements that help, I look for phrases such as “enzymes with a higher level of support to help inefficient digestion”. I also found phrases such as “enzymes that encourage proper nutrient absorption”. I looked for phrases, such as “aids in digestion of enzymes, carbohydrates and fats”. If you suffer chronically inflamed duodenum as I have since predeployment vaccines, your bile and enzyme duct may be too inflamed to inject necessary digestive juices and fat enzymes to slow digestion down after leaving the stomach.
      I found chewable papaya enzyme tabs I take AFTER each meal. And I found Apple Pectin with acidophilus capsules, which I can take before my meals. Anything you can dissolve in your mouth or under your tongue takes the work off your already compromised digestive tract.
      My doctors have said that apple pectin usually causes constipation in healthy people. I have never experienced constipation or a day without at least one bowel movement – even before I got sick. I cannot take grapefruit pectin because it diminishes effectiveness of Beta-blockers and blood pressure meds.
      I depend on fresh apples, pineapple, mangos and papayas as staple fruits I can tolerate and better absorb. I found a table that describes which enzymes help with what type of diarrhea –

      Arsenicum Album 6X HPUS for dark, offensive stool
      Podophyllum Pellets 6X HPUS for profuse, watery stool
      Chamomilla 6X HPUS for hot, green, watery stool
      Phosphorus 6X HPUS painless, copious, involuntary diarrhea
      Mercurius Viv. 6X HPUS greenish, slimy, painful stool

      Beware of diarrhea medications that contain Lactose N.F., especially if you are Lactose Intolerant or suffer dairy allergies.

  3. Sandy10m says:

    Hi Tracey,
    There is only one stool testing laboratory that I trust. They are THE specialists when it comes to finding the bad guys in our guts. Check out Parasitology Center in Scottsdale, Arizona. Order the Full GI kit and find out what you are fighting. Just knowing what you are up against (or not) will help you. I had a ranging Candida infection of my intestines for a long time. I figured out how to cure it (oral powdered Nystatin 3x day mixed in solution on empty stomach, with disciplined Paleo/Caveman diet), and now I am Candida-free. This lab will help you with a diagnosis and hopefully a solution.

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