Authors:	Zevallos, Victor F Yogev, Nir Hauptmann, Judith Nikolaev, Alexei Pickert, Geethanjali Heib, Valeska Fittler, Nicola Steven, Sebastian Luessi, Felix Neerukonda, Manjusha Janoschka, Claudia Tobinski, Ann-Marie Klotz, Luisa Waisman, Ari Schuppan, Detlef
Title:	Dietary wheat amylase trypsin inhibitors exacerbate CNS inflammation in experimental multiple sclerosis
Online publication date:	13-Mar-2024
Year of first publication:	2023
Language:	english
Abstract:	Objective: Wheat has become a main staple globally. We studied the effect of defined pro-inflammatory dietary proteins, wheat amylase trypsin inhibitors (ATI), activating intestinal myeloid cells via toll-like receptor 4, in experimental autoimmune encephalitis (EAE), a model of multiple sclerosis (MS). Design: EAE was induced in C57BL/6J mice on standardised dietary regimes with defined content of gluten/ATI. Mice received a gluten and ATI-free diet with defined carbohydrate and protein (casein/zein) content, supplemented with: (a) 25% of gluten and 0.75% ATI; (b) 25% gluten and 0.19% ATI or (c) 1.5% purified ATI. The effect of dietary ATI on clinical EAE severity, on intestinal, mesenteric lymph node, splenic and central nervous system (CNS) subsets of myeloid cells and lymphocytes was analysed. Activation of peripheral blood mononuclear cells from patients with MS and healthy controls was compared. Results: Dietary ATI dose-dependently caused significantly higher EAE clinical scores compared with mice on other dietary regimes, including on gluten alone. This was mediated by increased numbers and activation of pro-inflammatory intestinal, lymph node, splenic and CNS myeloid cells and of CNS-infiltrating encephalitogenic T-lymphocytes. Expectedly, ATI activated peripheral blood monocytes from both patients with MS and healthy controls. Conclusions: Dietary wheat ATI activate murine and human myeloid cells. The amount of ATI present in an average human wheat-based diet caused mild intestinal inflammation, which was propagated to extraintestinal sites, leading to exacerbation of CNS inflammation and worsening of clinical symptoms in EAE. These results support the importance of the gut-brain axis in inflammatory CNS disease.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-10189
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY-NC
Information on rights of use:	https://creativecommons.org/licenses/by-nc/4.0/
Journal:	Gut : an international journal of gastroenterology and hepatology 73 1
Pages or article number:	92 104
Publisher:	BMJ
Publisher place:	London
Issue date:	2023
ISSN:	1468-3288
Publisher DOI:	10.1136/gutjnl-2023-329562
Appears in collections:	DFG-491381577-H