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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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    Russ H

    Would be interesting to see whether vaccination against Strep. pneumoniae affects incidence of coeliac disease. In the UK, it has been given to infants since 2006 so I suppose any affect would have shown up by now.

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    Peteymoz
    On 6/7/2023 at 11:03 PM, Russ H said:

    Would be interesting to see whether vaccination against Strep. pneumoniae affects incidence of coeliac disease. In the UK, it has been given to infants since 2006 so I suppose any affect would have shown up by now.

    i have thought vaccines may be the root cause of this, i got all my medical records recently and was shocked to see how many vaccines i have been given as a little baby, my major complaint throughout my life has been skin problems, i now have celiac and have back and joint problems, probably all linked in my opinion

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    Scott Adams

    It is highly doubtful that your childhood vaccines are related in any way to your current health issues, and no link has ever been found between any vaccines and celiac disease. 

    @Russ H I would also be interested in more studies on whether the strep vaccine could have any effect on the incidence of celiac disease. This is a very interesting study that shows that some peoples' immune systems may be mistakenly targeting the 33-mer and p31-43 peptides in gluten as though they are strep.

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    PattyWayne

    So to my understanding you have the genes for Celiac, but with some people it takes something to activate it "a Pathogen"?  I know I had issues my entire life, with testing and testing because of stomach pain and others things-with being told it was nervous colitis and sensitive stomach, as a preteen.  It was not until searching for the cause of my arthritis, I talked with my doctor about me following a Keto diet to try to loose weight and after having a cheat meal of pizza how sick I got.  I tried again the following month with taco's with flour shells, same results.  I asked if I could develop a allergy to wheat, he tested me for Celiac and I came back positive for 3 out of the 4 test. It took 60 years, to understand I do not tolerate wheat and even small amounts make me horribly ill. 

    I too am wondering with Peteymoz if it could be "vaccine related"?  As a infant I was repeatedly given DTP, because I became so ill with each shot- I would miss the "window" for the booster and they said they had to start over- it was not until I almost died and was hospitalized it dawned on the Pediatrician I was reacting to the Tetanus. My Mother told me how colicky I was with different formulas long past when most babies no longer are, and how at 2, I would only eat Jell-O and peanut butter with a spoon.  Could it be as simple as vaccines?

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    Scott Adams

    No, there is no link to childhood vaccination and the incidence of celiac disease. The reason you probably never got diphtheria, tetanus, and pertussis is likely because you got this vaccine.

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    Peteymoz
    On 6/14/2023 at 6:30 PM, Scott Adams said:

    It is highly doubtful that your childhood vaccines are related in any way to your current health issues, and no link has ever been found between any vaccines and celiac disease. 

    @Russ H I would also be interested in more studies on whether the strep vaccine could have any effect on the incidence of celiac disease. This is a very interesting study that shows that some peoples' immune systems may be mistakenly targeting the 33-mer and p31-43 peptides in gluten as though they are strep.

    Robert F Kennedy jr said its probably caused by Glyphosate..... interesting that as i never read anything linking the two but a quick search finds a few articles on nih website this website and others, i said childhood vaccines as they do cause problems for most people and affect people differently so just my thought that they could cause a problem that over time if made worse through poor health/diet/lifestyle triggers celiac to start.

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    Scott Adams

    The articles we have on Glyphosate are summaries of published research. If there are any such articles on vaccines and celiac disease, we'll also summarize them, but until there is actual data that links the two, blind speculation like this isn't helpful to anyone.

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    PattyWayne
    On 6/15/2023 at 12:36 PM, Scott Adams said:

    No, there is no link to childhood vaccination and the incidence of celiac disease. The reason you probably never got diphtheria, tetanus, and pertussis is likely because you got this vaccine.

    The reason I have never have had Tetanus is because I get the Human tetanus immune gobulin  called Hypertet- it is what they use for active Tetanus.  Diphtheria, probably because I have not been anywhere I would have been exposed, and I did have Whooping Cough as a young child  (as well as my siblings)- at least that is what we have been told by my parents.  What I do have is a over active immune system that is attacking my body as a whole- and I have been told they believe there is a correlation from being over vaccinated with the DTP- putting me in a hyperimmune state. 

     

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    Scott Adams

    Please post scientific studies that support your comment that: "they believe there is a correlation from being over vaccinated with the DTP- putting me in a hyperimmune state". Who are "they," and the fact that people might believe something that has zero basis in fact would not surprise me at all. 

    As for Diptheria, it is possible to be exposed to diphtheria in the USA, although it is relatively rare due to widespread vaccination and public health measures. Diphtheria is a bacterial infection caused by Corynebacterium diphtheriae and can be transmitted through respiratory droplets from an infected person or by coming into contact with items contaminated with the bacteria. You are likely riding on the back of the herd vaccination rates of others, which makes it less likely for you to get it in the USA, as opposed to other countries with lower vaccination rates.

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    Russ H
    On 6/22/2023 at 2:42 PM, Peteymoz said:

    Robert F Kennedy jr said its probably caused by Glyphosate..... interesting that as i never read anything linking the two but a quick search finds a few articles on nih website this website and others, i said childhood vaccines as they do cause problems for most people and affect people differently so just my thought that they could cause a problem that over time if made worse through poor health/diet/lifestyle triggers celiac to start.

    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.

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    Wheatwacked
    On 6/14/2023 at 1:48 PM, PattyWayne said:

    but with some people it takes something to activate it "a Pathogen"? 

    23 hours ago, PattyWayne said:

    over active immune system that is attacking my body as a whole-

    What is your 25 hydroxy vitamin D blood level?  It is the vitamin that modulates the immune system and we have systematically been told that 29 ng/ml (72.5 nmol/L) is enough.  The normal level in an adult is 80 ng/ml. (200 nmol/L) and is set to maintain that level.

    But we are told to avoid sun for fear of skin cancer and not to take vitamin D supplements for fear of hypercalcemia.

    Low vitamin D lets the immune system rum amuck.  It is found in most sick people.  Just getting older is a risk factor.  Autoimmune diseases all have low D in common.  41% US adults have low D. 51% US adults have autoimmune disease. Think there might be a correlation?

    Supposistion: If your are already low vitamin D and you ger an infection, fighting the infection uses up more vitamin D leaving your immune system too depteted to manage.  Depending on your genetic makeup and what other essential nutrients you are deficient in, you get celiac, or thyroid or arthritis, or cancer, etc., and almost always osteopenia {40 million} or osteoporosis {10 million}.

    1. There are one million US adults living with Skin Cancer, purpotedly from too much UV radiation.
    2. There are 57 million US adults living with various autoimmune diseases with low vitamin D from avoiding UV radiation, and scared of supplementing enough, by the dire warnings of a very rare disease: hypervitaminosis D causing hypercalcemia.
    3. Quote

      The importance of body weight for the dose response relationship of oral vitamin D supplementation and serum 25-hydroxyvitamin D in healthy volunteers

      "We analyzed 22,214 recordings of vitamin D supplement use and serum 25(OH)D from 17,614 healthy adult volunteers participating in a preventive health program. This program encourages the use of vitamin D supplementation and monitors its use and serum 25(OH)D and serum calcium levels. Participants reported vitamin D supplementation ranging from 0 to 55,000 IU per day and had serum 25(OH)D levels ranging from 10.1 to 394 nmol/L [ 4 to 157 ng/ml ]. ... We did not observe any increase in the risk for hypercalcemia with increasing vitamin D supplementation. We recommend vitamin D supplementation be 2 to 3 times higher for obese subjects and 1.5 times higher for overweight subjects relative to normal weight subjects

       

    4. Quote

      Vitamin D and the Immune System

      Vitamin D can modulate the innate and adaptive immune responses. Deficiency in vitamin D is associated with increased autoimmunity as well as an increased susceptibility to infection. As immune cells in autoimmune diseases are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D deficient individuals with autoimmune disease may extend beyond the effects on bone and calcium homeostasis.

       

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    PattyWayne
    1 hour ago, Wheatwacked said:

    What is your 25 hydroxy vitamin D blood level?  It is the vitamin that modulates the immune system and we have systematically been told that 29 ng/ml (72.5 nmol/L) is enough.  The normal level in an adult is 80 ng/ml. (200 nmol/L) and is set to maintain that level.

    But we are told to avoid sun for fear of skin cancer and not to take vitamin D supplements for fear of hypercalcemia.

    Low vitamin D lets the immune system rum amuck.  It is found in most sick people.  Just getting older is a risk factor.  Autoimmune diseases all have low D in common.  41% US adults have low D. 51% US adults have autoimmune disease. Think there might be a correlation?

    Supposistion: If your are already low vitamin D and you ger an infection, fighting the infection uses up more vitamin D leaving your immune system too depteted to manage.  Depending on your genetic makeup and what other essential nutrients you are deficient in, you get celiac, or thyroid or arthritis, or cancer, etc., and almost always osteopenia {40 million} or osteoporosis {10 million}.

    1. There are one million US adults living with Skin Cancer, purpotedly from too much UV radiation.
    2. There are 57 million US adults living with various autoimmune diseases with low vitamin D from avoiding UV radiation, and scared of supplementing enough, by the dire warnings of a very rare disease: hypervitaminosis D causing hypercalcemia.
    3.  
    4.  

    Its low Vitamin D 25 Hydroxy 29.7 ng/mL and I take D3 125 MCG Daily.  I also have low B12 and 8 months ago was tested for Hemochromatosis because my arthritis was showing hooking in the bones of my fingers.  Tested double gene positive so every three months I have a slew of blood work including having Iron and Ferritin Level checked- Ferritin needs to stay in the 50 range or I have to have a phlebotomy. I also have Hashimoto's disease (found 30 years ago), which I take Levothyroxine daily.  And yes I have Osteopenia.  I have arthritis throughout my body....have had several back surgeries with lower lumbar fusion and a neck fusion, bad knees, shoulders.  Basically my body hates itself.  I also have Factor 7 & 8 - bleeding with clotting disorder which is also genetic from both my parents.  My Mother just died this past year from Liver cancer- which is leading my Hematologist to believe she also had Hemochromatosis and why he is staying right on top of things. What has been helpful in the last 5 years with them being able to test genetic markers for things and helping them get answers.  I am answering your questions because of you being so kind in asking me.

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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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