Authors:	Santos Guilherme, Malena dos Zevallos, Victor F. Pesi, Aline Stoye, Nicolai M. Nguyen, Vu Thu Thuy Radyushkin, Konstantin Schwiertz, Andreas Schmitt, Ulrich Schuppan, Detlef Endres, Kristina
Title:	Dietary wheat amylase trypsin inhibitors impact Alzheimer’s disease pathology in 5xFAD model mice
Online publication date:	18-Dec-2020
Year of first publication:	2020
Language:	english
Abstract:	Wheat amylase trypsin inhibitors (ATIs) represent a common dietary protein component of gluten-containing cereals (wheat, rye, and barley). They act as toll-like receptor 4 ligands, and are largely resistant to intestinal proteases, eliciting a mild inflammatory response within the intestine after oral ingestion. Importantly, nutritional ATIs exacerbated inflammatory bowel disease and features of fatty liver disease and the metabolic syndrome in mice. For Alzheimer’s disease (AD), both inflammation and altered insulin resistance are major contributing factors, impacting onset as well as progression of this devastating brain disorder in patients. In this study, we evaluated the impact of dietary ATIs on a well-known rodent model of AD (5xFAD). We assessed metabolic, behavioral, inflammatory, and microbial changes in mice consuming different dietary regimes with and without ATIs, consumed ad libitum for eight weeks. We demonstrate that ATIs, with or without a gluten matrix, had an impact on the metabolism and gut microbiota of 5xFAD mice, aggravating pathological hallmarks of AD. If these findings can be translated to patients, an ATI-depleted diet might offer an alternative therapeutic option for AD and warrants clinical intervention studies. Keywords: Aβ ATI 5xFAD gluten inflammation intestine
DDC:	540 Chemie 540 Chemistry and allied sciences 570 Biowissenschaften 570 Life sciences 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-5509
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	International journal of molecular sciences 21 17
Pages or article number:	6288
Publisher:	MDPI
Publisher place:	Basel
Issue date:	2020
ISSN:	1422-0067
Publisher URL:	https://doi.org/10.3390/ijms21176288
Publisher DOI:	10.3390/ijms21176288
Appears in collections:	JGU-Publikationen