Dietary Wheat Amylase Trypsin Inhibitors Impact Alzheimer’s Disease Pathology in 5xFAD Model Mice

International Journal of Molecular Sciences

NicolaiM. Stoye¹  VuThu Thuy Nguyen¹  Malena dos Santos Guilherme¹  Kristina Endres¹  Andreas Schwiertz²  Detlef Schuppan³  Aline Pesi³  VictorF. Zevallos³  Konstantin Radyushkin⁴  Ulrich Schmitt⁴ 

[1] Department of Psychiatry and Psychotherapy, University Medical Center Johannes Gutenberg-University, 55131 Mainz, Germany;Institute of Microecology, 35745 Herborn, Germany;Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center, 55131 Mainz, Germany;Leibniz Institute for Resilience Research, 55122 Mainz, Germany;

关键词: Aβ;    ATI;    5xFAD;    gluten;    inflammation;    intestine;   

DOI  :  10.3390/ijms21176288

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown