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Gluten grains

GLUTEN & AUTOIMMUNITY

Gluten is a protein found naturally within wheat seeds.  A wheat kernel contains 8%–15% protein, of which 10%–15% is albumin/globulin and 85%–90% is gluten.  Gluten is found in wheat (wheat berries, durum, emmer, semolina, spelt), Rye, Barley, Malt, Brewers Yeast and Wheat Starch. Certain foods such as dairy, oats, yeast, coffee, sesame, millet corn, rice have been shown to cross react with gluten due to similar amino acid structures.

Gluten is a complex mix of proteins, mainly gliadin and glutenin.  Gluten is  stable at high temperatures, acts as a binding agent and is used in baking (bread, cakes for texture and elasticity but is also found in many processed foods. Therefore, less obvious sources of gluten include processed meat and meat substitutes; gelling agents, thickeners or emulsifiers in confectionary, ice cream, seasonings, dressings, stuffing and marinades; and as fillers and coatings used in medications.  

New variants of wheat due to mechanisation of farming, the growing use of pesticides and fertilisers and the shorter bread leavening process causing an increased concentration of toxic gluten peptides in bakery products may all play a role in adverse immunologic reactions to gluten.

Gliadin protein contains peptide sequences (called epitopes) that are very resistant to the digestive process, escaping breakdown in the human gut. This complexity of digestion is due to gliadin's high amount of the amino acids called proline and glutamine, which many digestive enzymes are unable to breakdown.  Since gluten may be only partially broken down, this can cause havoc in the digestive system especially as these large particles can cause leaky gut. 

Gluten peptides are well researched to be immunogenic and can trigger T-cell immune reactivity.  Gluten is well studied to be a cause of Autoimmune Celiac Disease by initiating an immune response causing mucosal inflammation, small intestinal atrophy of the villi, and increased gut permeability.  Celiac disease can occur in genetically pre-disposed individuals carrying the (HLA)-DQ2 or DQ8 genes.  A gluten free diet is essential in this case.  Other Autoimmune diseases associated with gluten exposure are gluten ataxia and dermatitis herpetiformis.  Wheat allergy is an IgE-mediated reaction to the insoluble gliadins of wheat. The symptoms usually develop within minutes after ingestion and include itching and swelling, skin rash, and life-threatening anaphylaxis.  Debate remains around whether the gluten proteins can trigger symptoms in patients with no features of coeliac disease, ie non-coeliac gluten sensitivity.  Nonceliac gluten sensitivity is diagnosed in individuals who do not have celiac disease or wheat allergy but who have intestinal symptoms, extra-intestinal symptoms, or both, related to ingestion of gluten-containing grains, with symptoms improving on elimination. Since gluten can cause symptoms in patients with gluten sensitivity dietary elimination remains an effective management strategy.  It is important to note that elimination for a minimum of 3-6 months is required to see the benefit.  Lab testing can conclude whether antibodies are raised to gliadin or wheat proteins maybe causing sensitivity.

Gluten induced dysbiosis, increased intestinal permeability, enteric and systemic side effects, cross-reactive antibodies, and the sequence of homologies between brain antigens and gluten are all to be considered in current research and implicated in Autoimmunity. Molecular mimicry, may allude to some autoimmune aspects between gluten and neurodegenerative disease, circulating systemically, being localized in the brain and being a prime substrate for tissue damage.

 Cross-Reactivity between Wheat/Gluten and Brain Tissue Components

'A schematic presentation of cross-reactive antibodies between two separated antigenic determinants. The specific antibody that reacted with each is cross-reacting to both of them. (A) Anti-gluten/gliadin antibodies. (B) Anti-brain autoantibodies. (C) Anti-gluten/gliadin and brain epitopes cross-reactive antibodies'.


Reference: (Lerner A, Benzvi C., 2021)

doi.org/10.3390/cells10040756

Cross reactivity wheat and brain
Brain gut axis

The gluten–brain relationship that might operate in neurodegenerative diseases 

'Ingested gluten and gliadin’s peptides cross talks with brain epitopes in neurodegenerative diseases.

(A) Wheat reach gluten is ingested and digested to gliadin peptides.

(B) By deamidation and cross-linking, luminal and mucosal tissue and microbial transglutaminases post translate those peptides to immunogenic molecules.

(C) In parallel, gluten affects the microbiome/dysbiome ratio, resulting in proinflammatory metabolome and harmful microbial constituents.

(D) This mobilome finds its way, trans- or inter-enterocytically, through the failed tight junction to end up sub-epithelially.

(E) In addition, the sensing epithelial and subepithelial cells are activated and deliver signals to the adjacent local or systemic blood, lymphatic and neuronal networks (E,F), respectively.

(G) Finally brain neuroinflammatory and neurodegenerative processes are affected'.

Reference: (Lerner A, Benzvi C., 2021)

 doi.org/10.3390/cells10040756

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