Dietary wheat amylase trypsin inhibitors impact alzheimer’s disease pathology in 5xfad model mice

Malena Dos Santos Guilherme, Victor F. Zevallos, Aline Pesi, Nicolai M. Stoye, Vu Thu Thuy Nguyen, Konstantin Radyushkin, Andreas Schwiertz, Ulrich Schmitt, Detlef Schuppan*, Kristina Endres

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
24 Downloads (Pure)


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.

Original languageEnglish
Article number6288
Number of pages17
JournalInternational Journal of Molecular Sciences
Issue number17
Publication statusPublished - 31 Aug 2020


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