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  • Jefferson Adams
    Jefferson Adams

    Celiac Patients Tolerate Wheat Spaghetti After Hookworm Treatment

    Reviewed and edited by a celiac disease expert.

    Celiac.com 10/03/2014 - Celiac disease patients in Australia have shown a major improvement in gluten tolerance after receiving experimental hookworm treatments. The study is part of an effort to determine if parasitic helminths, such as hookworm, might help to treat inflammatory disorders, including celiac disease.

    Photo: Nnaluci--Wikimedia CommonsIn this case, the research team assessed the influence of experimental hookworm infection on the predicted outcomes of three escalating gluten challenges in volunteers with confirmed celiac disease.



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    The research team included John Croese, MD, Paul Giacomin, PhD, Severine Navarro, PhD, Andrew Clouston, MD, Leisa McCann, RN, Annette Dougall, PhD, Ivana Ferreira, BSc, Atik Susianto, MD, Peter O'Rourke, PhD, Mariko Howlett, MD, James McCarthy, MD, Christian Engwerda, PhD, Dianne Jones, BHSc, and Alex Loukas, PhD.

    They are variously affiliated with the Department of Gastroenterology and Hepatology at The Prince Charles Hospital, Brisbane, Australia, the Center for Biodiscovery and Molecular Development of Therapeutics at the Australian Institute of Tropical Health and Medicine of James Cook University in Cairns, Australia, Envoi Specialist Pathologists in Brisbane, Australia, QIMR Berghofer Medical Research Institute in Brisbane, Australia, the Royal Brisbane and Women's Hospital, and with Logan Hospital, Brisbane, Australia.

    This particular study followed twelve adult volunteers with diet-managed celiac disease. The volunteers were inoculated with 20 Necator americanus (hookworm) larvae, and then consumed increasing amounts of gluten in the form of spaghetti.

    The volunteers first received 10 to 50 milligrams for 12 weeks (microchallenge); they then received 25 milligrams daily + 1 gram twice weekly for 12 weeks (GC-1g); and finally 3 grams daily (60-75 straws of spaghetti) for 2 weeks (GC-3g).

    The subjects were then evaluated for symptomatic, serologic, and histological outcomes of gluten toxicity. They were also examined for regulatory and inflammatory T cell populations in blood and mucosa. Two gluten-intolerant subjects withdrew after micro-challenge. Ten completed GC-1g, and eight of these ten volunteers enrolled in and completed the full course of the study.

    Most celiacs who are exposed to gluten challenge will show adverse changes in the intestinal villi, which is measured in terms of villous height-to-crypt depth ratios. Also, such patients will usually show an increase in blood antibodies, such as IgA-tissue transglutaminase, indiucating an adverse reaction to gluten. However, the results here showed that median villous height-to-crypt depth ratios (2.60-2.63; P = .98) did not decrease as predicted after GC-1g. Moreover, mean IgA-tissue transglutaminase titers declined, contrary to the predicted rise after GC-3g.

    Other results showed that quality of life scores improved (46.3-40.6; P = .05); while celiac symptom indices (24.3-24.3; P = .53), intra-epithelial lymphocyte percentages (32.5-35.0; P = .47), and Marsh scores remained unchanged by gluten challenge.

    Intestinal T cells expressing IFNγ were reduced following hookworm infection (23.9%-11.5%; P = .04), with corresponding increases in CD4+ Foxp3+ regulatory T cells (0.19%-1.12%; P = .001).

    Hookworms in the form of Necator americanus promoted tolerance and stabilized, or improved, all tested measures of gluten toxicity in volunteers with celiac disease. So, after being voluntarily infected with 20 hookworms, these celiac disease volunteers were able to eat increasingly large amounts of gluten with none of the usual changes or adverse symptoms.

    Could hookworm treatments represent the future of treatment for celiac disease, and maybe other inflammatory conditions? Clearly, further tests are needed to determine exactly how safe it is for celiac patients receiving this treatment to eat gluten. So far, however, the future looks bright.

    What do you think? If swallowing a small dose of hookworms would eliminate your adverse reactions, and allow you to safely eat gluten, would you do it?

    The radio program Radiolab has an interesting segment on hookworm, which you can stream here: Radiolab

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    Absolutely, I would do this. I'd actually stay gluten free, but to guard against cross contamination, for sure. I've had three airborne glutenings in the last year, two in grocery stores where I was not near the bakery or flour aisle, one in a building where drywall was being used unbeknownst to me in another part of the building. Day to day life is dangerous for me right now, and if this makes it less so, give me a plate of hookworms, or anything!

    Drywall? Can you please elaborate on drywall. We are about to begin removing the plaster walls in our 1840 home and replace them with drywall. Now you have me a bit worried. I am a 0 ppm celiac, I get sick like you from airborne glutenings. I also get the dermatitis (something the so-called experts say you don't get if you have the intestinal issues, wrong!) from airborne and contact glutenings.

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    Hook worms can kill you. No thanks.

    Hookworms cannot kill humans. The only negative side effect of hookworm is anemia. That only occurs if there are a large amount of hookworms in the gut. Anemia is slow to develop, easy to spot and easy to cure. In places where there is no access to medical care, anemia can be life threatening, but that is extremely unlikely in a western medical setting.

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    It is no surprise that we don't have a cure for this by now. Every time an article shows up about a possible way to help people with celiac disease eat gluten again everybody comments how they would never in a million years try it. Gluten is evil and they love gluten-free food. You never see this with people who cannot eat peanut butter, shellfish, or any of the other million disorders out there.

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    It is no surprise that we don't have a cure for this by now. Every time an article shows up about a possible way to help people with celiac disease eat gluten again everybody comments how they would never in a million years try it. Gluten is evil and they love gluten-free food. You never see this with people who cannot eat peanut butter, shellfish, or any of the other million disorders out there.

    An excellent point.

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    My instant reaction is that it is not worth eating gluten in order to swallow something that my have unknown consequences. The only benefit would be to alleviate cross contamination and be able to eat out with more ease. My question is that there had to be some information to make the doctors think in the first place that hookworms would help with celiac. What could they have previously discovered that would merit this study?

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  • About Me

    Jefferson Adams

    Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,500 articles on celiac disease. His coursework includes studies in science, scientific methodology, biology, anatomy, medicine, logic, and advanced research. He previously served as SF Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.


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    Scott Adams
    Celiac.com 2/13/2003 - This new study emphasizes the importance of following a strict gluten-free diet, and getting regular follow-up biopsies after your diagnosis. It also speaks to the need to discover whether or not you may have additional food intolerance, such as to cows milk (casein), soy, corn, etc., as some of these can also cause intestinal damage similar to that of celiac disease. -Scott Adams

    Lee SK, Lo W, Memeo L, Rotterdam H, Green PH.
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    Current affiliations: Department of Surgical Pathology and Medicine, Columbia University College of Physicians and Surgeons, New York, New York.
    BACKGROUND: The diagnosis of celiac disease requires characteristic histopathological changes in an intestinal biopsy with clinical improvement in response to a gluten-free diet. Endoscopy with procurement of biopsy specimens is often performed to document response to the diet, but there are little data on the appearance of treated celiac disease. This study examined the endoscopic and histopathological appearance of the duodenum of patients with celiac disease whose diet was gluten-free.
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    Jefferson Adams
    Celiac.com 11/16/2009 - Could unknown benefits from one of the oldest parasites of the human digestive tract hold the key to cure for celiac disease?
    Australian scientists think so. Encouraged by successful treatments of Crohn's and ulcerative colitis by American researchers using a pig whipworm (Trichuris sues), a team of Australian researchers is recruiting volunteers with celiac disease for trials using human hookworm (Necator americanus).
    The researchers have undertaken a similar preliminary study using a human hookworm in Crohn's patients.
    Researchers hypothesize that the disappearance of intestinal parasites from humans in developed countries may be responsible for the upsurge in many diseases including Celiac Disease, Crohn's, ulcerative colitis, asthma and hay fever.
    Using a small group of healthy people with celiac disease, the investigators will look to see if human hookworm interferes with the human immune reaction to gluten.
    Parasites survive partly by interfering with the host's immune response. The mechanisms they use to accomplish this are similar to those required by a person to regulate against the so-called autoimmune disorders, wherein the body begins to fight against itself.
    The investigators suspect that when parasites are excluded from the environment, some individuals become sufficiently self-reactive to develop an autoimmune disease.
    Using a small group of healthy people with celiac disease, the investigators will test if a human hookworm, Necator americanus, inhibits immune responsiveness to gluten.
    Specifically, they will examine whether hookworm infection will change the immune processes and suppress gluten sensitivity in people with celiac disease.
    Celiac disease is a good model for studying Crohn's disease because both involve similar immune changes. However, celiac patients are usually healthier overall, and, importantly, are not taking powerful immune suppressive drugs, and the provocative antigens (molecules that engage the immune system and provoke the disease) are well known and can be administered or cut out at will.
    In addition to directly benefitting celiac disease sufferers, this study may provide potential guidance in the use of hookworms to control inflammatory bowel disease.
    The study is open to people with proven celiac disease who reside in Brisbane, Australia. Those who enroll will be required to avoid gluten for six months.
    The blinded study will compare disease activity and immunity after a controlled break from the gluten-free diet in celiac patients, before and after hookworm infection.
    The team will use conventional and experimental methods to examine the disease severity and the immune system of celiac subjects before and after being inoculated with N. americanus.
    They will then compare immunity levels of the study subjects
    against those of matched, celiac control subjects (not infected with hookworm), before and after eating four pieces of standard white bread each day for three to five days.
    The initial study group will be small. The researchers will recruit ten subjects for each arm of the study, for a total of twenty.
    Initially, ten larvae will be placed on the skin under a light dressing for thirty minutes, followed by five more after twelve weeks.
    The researchers intend to asses whether the hookworm infection will change the immune processes and suppress gluten sensitivity in people with celiac disease. Outcomes to be measured will be those that reflect the activity of celiac disease.
    Stay tuned to see if hookworm therapy will be coming to a gastroenterologist near you! Tell us what you think. Would you sign up? Comment below.
    Source:
    ClinicalTrials.gov



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