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Dietary wheat amylase trypsin inhibitors exacerbate CNS inflammation in experimental multiple sclerosis.
Across the world, wheat has become a staple food. In a C57BL/6J murine model of experimental autoimmune encephalitis (EAE) induced for the study of multiple sclerosis (MS), Zevallos et al. (2024) investigated the impact of specific pro-inflammatory dietary proteins, wheat amylase trypsin inhibitors (ATI), on stimulating intestinal myeloid cells via toll-like receptor 4. C57BL/6J mice were given controlled diets containing a specified amount of gluten/ATI to induce EAE. A specified carbohydrate and protein (casein/zein) diet free of gluten and ATI was fed to the mice, along with supplements of either (a) 25% gluten and 0.75% ATI, (b) 25% gluten and 0.19% ATI, or (c) 1.5% pure ATI. The impact of dietary ATI on intestinal, splenic, mesenteric lymph node, and central nervous system (CNS) subsets of lymphocytes and myeloid cells, as well as on the clinical severity of EAE, was examined. Peripheral blood mononuclear cells from controls and MS patients were monitored for activation. The authors observed that when mice were fed dietary ATI in a dose-dependent manner, their EAE clinical scores were much more significant than when fed alternative diets, including gluten alone. The rise in the numbers and activation of CNS-infiltrating encephalitogenic T-lymphocytes and pro-inflammatory intestinal, splenic, lymph node, and CNS myeloid cells was identified as the mediating factor. Peripheral blood monocytes from MS patients and healthy controls were stimulated by ATI as predicted. Dietary wheat was found to activate both Human and murine myeloid cells through ATI content. The average wheat-based diet’s level of ATI produced moderate intestine inflammation that spread to extraintestinal locations, aggravating CNS inflammation and making EAE patients’ clinical symptoms worse. The authors highlight the role of the gut-brain axis in CNS inflammatory illnesses [NPID: Wheat, intestinal inflammation, diet, animal model, Experimental Autoimmune Encephalitis, Multiple Sclerosis]
Year: 2024
