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Wheat Amylase-Trypsin Inhibitors Promote Intestinal Inflammation via Activation of Myeloid Cells

Discussion in 'Other Health News and Research' started by hixxy, Jan 7, 2017.

  1. hixxy

    hixxy Senior Member

    Nutritional Wheat Amylase-Trypsin Inhibitors Promote Intestinal Inflammation via Activation of Myeloid Cells.

    Zevallos VF, Raker V, Tenzer S, Jimenez-Calvente C, Ashfaq-Khan M, Rüssel N, Pickert G, Schild H, Steinbrink K, Schuppan D.


    Wheat amylase-trypsin inhibitors (ATIs) are nutritional activators of innate immunity, via activation of the toll like receptor 4 (TLR4) on myeloid cells. We aimed to characterize the biologic activity of ATIs in various foods and their effect on intestinal inflammation.

    We selected 38 different gluten-containing and gluten-free products, either unprocessed (such as wheat, rye, barley, quinoa, amaranth, soya, lentils, and rice) or processed (such as pizza, pasta, bread, and biscuits). ATIs were extracted and their biological activities determined in TLR4-responsive mouse and human cell lines. Effects of oral ATIs on intestinal inflammation were determined in healthy C57BL/6 mice on a gluten-free or ATI-free diet and in mice given low-level polyinosinic:polycytidylic acid or dextran sodium sulfate, to induce colitis. Parameters of innate and adaptive immune activation were determined in duodenum, ileum, colon, and mesenteric lymph nodes.

    Modern gluten-containing staples had levels of TLR4-activating ATIs that were as much as 100-fold higher than in most gluten-free foods. Processed or baked foods retained ATI bioactivity. Most older wheat variants (such as Emmer or Einkorn) had lower bioactivity than modern (hexaploid) wheat. ATI species CM3 and 0.19 were the most prevalent activators of TLR4 in modern wheat, and were highly resistant to intestinal proteolysis. Their ingestion induced modest intestinal myeloid cell infiltration and activation, and release of inflammatory mediators-mostly in the colon, then in the ileum and then in the duodenum. Dendritic cells became prominently activated in mesenteric lymph nodes. Concentrations of ATIs found in a normal daily gluten-containing diet increased low-level intestinal inflammation.

    Gluten-containing cereals have by far the highest concentrations of ATIs that activate TLR4. Orally ingested ATIs are largely resistant to proteases and heat, and increase intestinal inflammation by activating gut and mesenteric lymph node myeloid cells.

    Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

    celiac disease; digestion; gluten; wheat sensitivity

    PMID: 27993525
    DOI: 10.1053/j.gastro.2016.12.006

    natasa778, adreno, alex3619 and 3 others like this.
  2. hixxy

    hixxy Senior Member

    There was already an article on this posted here back in October which I'd since forgotten about until now. Actual research paper not published until last month.
    alex3619 likes this.
  3. ebethc

    ebethc Senior Member

    am I interpreting this correctly? my take: modern gluten (and maybe similar proteins) shut down or inactivate trypsin.

    I'm doing research on trypsin this week, so this caught my eye... Trypsin (in wobenzym, vascuzyme, etc) helps break down circulating immune complexes and thus reduces inflammation. if I'm understanding this correctly, then this could be one of the mechanisms that leads to inflammation for me...

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