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  • Jefferson Adams
    Jefferson Adams

    Gluten and Pathogens Connection Holds Implications for Celiac Disease and Gluten-Related Disorders

    Reviewed and edited by a celiac disease expert.

    Researchers conducted a comprehensive analysis of the two most significant gluten peptides involved in celiac disease: the 33-mer and p31-43 gliadin peptides. Here's what they found.

    Gluten and Pathogens Connection Holds Implications for Celiac Disease and Gluten-Related Disorders - Streptococcus pneumoniae. Image: CC BY 4.0--Debbie Marshall
    Caption: Streptococcus pneumoniae. Image: CC BY 4.0--Debbie Marshall

    Celiac.com 06/05/2023 - Gluten-related disorders involve immune responses triggered by gluten ingestion, and they affect millions of individuals worldwide. With an overall prevalence of about 5%, gluten-related disorders represent a potentially significant health concern. The most prominent gluten-related disorder is celiac disease, a T-cell-mediated autoimmune disease with a wide range of symptoms, including diarrhea, malabsorption, and even lymphoma. 

    Despite extensive research on gluten-related disorders, the environmental factors that contribute to the diverse reactions in susceptible individuals have remained elusive. However, recent studies have shed light on a potential link between pathogens and the development of celiac disease, transcending the traditional notion of molecular mimicry.

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    Scientists have long speculated that pathogens might act as environmental triggers for celiac disease by exploiting molecular mimicry mechanisms. Molecular mimicry happens when foreign molecules resemble self-antigens, leading to immune system confusion and subsequent attacks on host tissues. In this context, it is plausible that pathogens may exhibit molecular, structural, and physical similarities to gluten, thereby inducing immune responses in susceptible individuals.

    Analysis of the 33-mer and p31-43 Gliadin Peptides

    To investigate this hypothesis further, researchers conducted a comprehensive analysis of the two most significant gluten peptides involved in celiac disease: the 33-mer and p31-43 gliadin peptides. 

    The research team included Diego S. Vazquez, Hanna M. Schilbert, and Veronica I. Dodero, Francesco Asnicar, Academic Editor and Serena Manara. They are variously affiliated with the Grupo de Biología Estructural y Biotecnología (GBEyB-IMBICE), Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina; the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) in Buenos Aires, Argentina.

    Streptococcus Pneumoniae and Granulicatella sp. Show Strong Similarity to the Gliadin Peptides

    Employing advanced bioinformatics techniques, the team performed a stringent BLASTp search, and identified high sequence similarity regions between these gliadin peptides and proteins derived from bacterial pathogens. Notably, extracellular proteins from Streptococcus pneumoniae and Granulicatella sp. displayed a strong similarity to the gliadin peptides.

    Further examinations involved molecular dynamics calculations and the construction of updated α-2-gliadin models. These investigations revealed close spatial localization and solvent-exposure of the 33-mer and p31-43 peptides. 

    By comparing these structures with the homology models and localization predictors of pathogen-related proteins, the researchers identified putative functions of the pathogen-derived sequences, such as T-cell epitopes and SH3/WW-binding domains. Moreover, shape and size parallels between the pathogenic agents and the superstructures of gliadin peptides led to the formulation of novel hypotheses concerning the activation of innate immunity and dysbiosis. 

    The researchers propose that these pathologically relevant gluten-derived peptides may behave as non-replicating pathogens, introducing exciting avenues for further exploration at the intersection of innate immunity, microbiome research, and the field of food science.

    Conclusions

    These findings suggest that the relationship between gluten and pathogens is more intricate than previously understood. The sequence, structural, and physical similarities between gluten peptides and pathogen-derived proteins raise intriguing questions about the role of pathogens in the development of gluten-related disorders. 

    While the molecular mimicry hypothesis remains relevant, this research expands the scope of investigation, highlighting the need to consider a broader range of factors that may contribute to the activation of the immune system in individuals susceptible to celiac disease.

    By unraveling the mechanisms behind the immune responses triggered by gluten ingestion, researchers are helping to improve diagnosis, treatment, and prevention strategies for celiac disease and other gluten-related disorders. 

    Read more in the Int J Mol Sci. 2021 Sep; 22(17): 9278


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    Peteymoz
    7 hours ago, Russ H said:

    I doubt that very much. Robert F Kennedy jr. has no scientific or medical qualifications and promotes conspiracy theories and anti-vaccine propaganda. Childhood vaccines do not cause problems for most people - they are thoroughly tested and monitored and are very safe. It is not known what triggers coeliac disease.

    The allegation that glyphosphate causes coeliac disease comes from a nonsensical publication in the journal Interdisciplinary Toxicology. One of the authors is an 'independent scientist', the other a computer scientist. No actual evidence is presented.

    please show those studies then from fda cdc or nih. rfk may not be a scientist but that does not mean the things he says should be ignored or marginalized 90% of the people commenting on this site are not scientists but there comments and advice have helped countless people with celiac improve there illness and quality of life so not being a scientist but talking about science issues does not mean your wrong or conspiracy theorist. 🙄

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    Russ H
    3 hours ago, Peteymoz said:

    please show those studies then from fda cdc or nih. rfk may not be a scientist but that does not mean the things he says should be ignored or marginalized 90% of the people commenting on this site are not scientists but there comments and advice have helped countless people with celiac improve there illness and quality of life so not being a scientist but talking about science issues does not mean your wrong or conspiracy theorist. 🙄

    People here a posting rigorous scientific consensus backed information. Kennedy is not.

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    Wheatwacked
    5 hours ago, PattyWayne said:

    Its low Vitamin D 25 Hydroxy 29.7 ng/mL and I take D3 125 MCG Daily. 

    Than for your answer. You make my case.

    I have been taking 250 mcg every day since 2015.  At first I was cautious and started at 25 mcg, believing in the fear, increased each week. At 200 mcg, still no fireworks, but a few days at 250, my whole mood changed.  A light turned on and I understood "Sunshine in a bottle".  Sept 2018 it was 44.7 ng/m (112 nmol/L). August 2021 it got as high as 86.9 ng/ml (218 nmol/L) and since then has never gone above.

    Back to my friend Choline.  A close association of abnormal iron metabolism with steatosis in the mice fed a choline-deficient diet .  Less than 10% of western diet eaters get enough. Especially if you follow the the advice from the 70's to reduce liver, egg and beef consumption.  3 eggs a day or 10 cups of cooked broccoli for the DV.  Choline is absorbed in the small intestine, so combined with diet, malabsorption due to Celiac Disease will kill you.  Other symptoms of low choline are high homocysteine, cardiovascular inflammation, brain fog, gall bladder disease symptoms, and neural tube defects in utero and Non Alcoholic Fatty Liver NFLD. 

    Ascorbic acid may be detrimental to individuals who carry the gene for hemochromatosis.

    Vitamins that can help with hemochromatosis are coincidentally the same ones that methylate homocysteine, ie., B12, B6, Folate, Choline and Taurine.  Extra nutrients specifically to help make  hemoglobin and red blood cells

    Quote

    Studies in patients receiving long-term TPN [total parenteral nutrition] have shown that low levels of plasma choline are common and can be associated with hepatic steatosis. Treatment of these patients with oral administration of choline improved plasma levels and decreased hepatic fat content;  Essential nature of choline with implications for total parenteral nutrition

    In short, you may have long term unrecognized nutrient malnutrition which exasperates your genetic tendencies.  In America we don't have malnutrition, just diseases and symptoms; and there are pills to shut them down for that.

    You are what you don't eat.

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    Peteymoz
    3 hours ago, Russ H said:

    People here a posting rigorous scientific consensus backed information. Kennedy is not.

    just because there is a concensus doesnt make it right or fact, the world used to be flat, the earth used to be the centre of the universe and also the only place where life exists, all concensus is in my opionion is a closed group dictating something and locking it out for challenge or scrutiny and the closing of the door of open mindedness. i take the approach of anything is possible until it can be proven otherwise and until then its open season and even afterwards it can still be challanged because untill we know everything about everything we still cant say its settled.

    if i took my doctors concensus (3 seperate gp's) i would still be treating celiac disease as it was ibs which are two different things, how many people have had the same if not worse for far longer? i have read so many comments on this site of people saying they have been mis diagnosed multiple times by different doctors for years, my constant challanging has got me this far years later and im still challanging them and myself by reading as much as i can about this disease and food eating habits, diets, food types and groups, e numbers and cooking practices and all that. my knowledge or info will never be fulfilled on this subject i will learn new things all the time through this site and others.

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    PattyWayne
    1 hour ago, Wheatwacked said:

    Than for your answer. You make my case.

    I have been taking 250 mcg every day since 2015.  At first I was cautious and started at 25 mcg, believing in the fear, increased each week. At 200 mcg, still no fireworks, but a few days at 250, my whole mood changed.  A light turned on and I understood "Sunshine in a bottle".  Sept 2018 it was 44.7 ng/m (112 nmol/L). August 2021 it got as high as 86.9 ng/ml (218 nmol/L) and since then has never gone above.

    Back to my friend Choline.  A close association of abnormal iron metabolism with steatosis in the mice fed a choline-deficient diet .  Less than 10% of western diet eaters get enough. Especially if you follow the the advice from the 70's to reduce liver, egg and beef consumption.  3 eggs a day or 10 cups of cooked broccoli for the DV.  Choline is absorbed in the small intestine, so combined with diet, malabsorption due to Celiac Disease will kill you.  Other symptoms of low choline are high homocysteine, cardiovascular inflammation, brain fog, gall bladder disease symptoms, and neural tube defects in utero and Non Alcoholic Fatty Liver NFLD. 

    Ascorbic acid may be detrimental to individuals who carry the gene for hemochromatosis.

    Vitamins that can help with hemochromatosis are coincidentally the same ones that methylate homocysteine, ie., B12, B6, Folate, Choline and Taurine.  Extra nutrients specifically to help make  hemoglobin and red blood cells

    In short, you may have long term unrecognized nutrient malnutrition which exasperates your genetic tendencies.  In America we don't have malnutrition, just diseases and symptoms; and there are pills to shut them down for that.

    You are what you don't eat.

    That sound very interesting.  I am unable to eat eggs due to allergy. Gall bladder was  removed years ago, bile was crystalized. I get a shot of B12 every 3 months but willing to increase vit D and if you think  getting methylate homocysteine, ie., B12, B6, Folate, Choline and Taurine would help me, honestly willing to try to feel better.  Thank you.

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    Wheatwacked

    PattyWayne, sorry to hear about your gallbladder.  I am not a health professional, but yes I think they would help.

    Double the D.  If at 125 mcg you are still only 29 you need more. Or more unprotected sunlight.  

    Choline supplements include choline bitartrate, phosphatidylcholine, and lecithin.  RDA is about 500 mg a day, Tolerable Safe Upper Limit is 3500 mg and side effects (low BP) don't appear to be a problem unless you take around 7000 mg a day.  Choline Fact Sheet for Health Professionals

    I take 840 mg a day of phosphatidylcholine, equivalent to 500 mg choline.

    Taurine is an essential amino acid that works as a strong antioxidant especially against oxidative stress in the eye.  Like choline we make some, but not enough, and heavily recycle it. Sick people need more. Taurine: A “very essential” amino acid

    Even with sufficient intake to store up B vitamins they are only stored for a few weeks. Those shots last for 48 to 72 hours.  Leaving you difficient 2 months and 27 days.  I take 1000 mcg once a day and much cheaper.

    If you can get a homocysteine blood test it is considered an independant indicator of cardiovascular inflammation. It is not rare but apparently It isn't commonly done. 

    Except for folic acid (upper limit 1000 mg) there is no upper limit set for the B vitamins. Folate from food has no upper limit.  Legally though the words on labels folic acid and folate are the same thing. B3 (Nicotinic Acid) will cause flushing at first. Simpler and quicker to take them from bottles.  I take 500 a day each of B1, B3, B5 with the B12, choline and taurine.  lost my belly fat and got energy.  My homocysteine was 14 mcmol/L last month. Range is <18. And my family is rife with heart disease, hyperlipidemia.

    For food: Primarily I eat two parts Garden salad to one part proteins like farm raised salmon, ground beef, etc. Has a lower omega 6 to 3 ratio, The standard american diet with gluten comes in at 20:1 where optimum health is < 3:1.  That's why so many need omega 3 supplements. In short omega 6 is inflammatory and omega 3 is healing.

    More stuff on D from Surge of information on benefits of vitamin D

    • A lifeguard study that found vitamin D levels in the 70 ng/mL range up to 100 ng/mL (nature’s level) were associated with no adverse effects;
    • Data in patients with breast cancer showing a reduction in the incidence of new cancer with postulated 0 point at 80 ng/mL;
    • Colon cancer data showing a reduction in the incidence of new cancer (linear) with postulated 0 point at 75 ng/mL;
    • More than 200 polymorphisms of the vitamin D receptor requiring higher D levels to attain same desired outcomes;
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    Scott Adams
    On 6/27/2023 at 8:00 AM, Peteymoz said:

    just because there is a concensus doesnt make it right or fact, the world used to be flat, the earth used to be the centre of the universe and also the only place where life exists, all concensus is in my opionion is a closed group dictating something and locking it out for challenge or scrutiny and the closing of the door of open mindedness. i take the approach of anything is possible until it can be proven otherwise and until then its open season and even afterwards it can still be challanged because untill we know everything about everything we still cant say its settled.

    if i took my doctors concensus (3 seperate gp's) i would still be treating celiac disease as it was ibs which are two different things, how many people have had the same if not worse for far longer? i have read so many comments on this site of people saying they have been mis diagnosed multiple times by different doctors for years, my constant challanging has got me this far years later and im still challanging them and myself by reading as much as i can about this disease and food eating habits, diets, food types and groups, e numbers and cooking practices and all that. my knowledge or info will never be fulfilled on this subject i will learn new things all the time through this site and others.

    But the Earth was never flat or the center of our universe, and only ignorance and religious dogma kept European populations in the dark on these things—thus the “dark ages.” It took brave people using science during the Enlightenment to prove this, but I don’t see how your comments are related to this article. Don't act like there isn't an objective truth out there and all ideas are equal because there is generally a scientifically verifiable truth, and not all ideas/hypotheses are equal.

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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. His articles, essays, poems, stories and book reviews have appeared in numerous magazines, journals, and websites, including North American Project, Antioch Review, Caliban, Mississippi Review, Slate, and more. He is the author of more than 2,500 articles on celiac disease. His university coursework includes studies in science, scientific methodology, biology, anatomy, physiology, medicine, logic, and advanced research. He previously devised health and medical content for Colgate, Dove, Pfizer, Sharecare, Walgreens, and more. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of numerous books, including "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

    >VIEW ALL ARTICLES BY JEFFERSON ADAMS

     


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