{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:43:12Z","timestamp":1777502592135,"version":"3.51.4"},"reference-count":70,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T00:00:00Z","timestamp":1598832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008454","name":"Boehringer Ingelheim Stiftung","doi-asserted-by":"publisher","award":["BIF04"],"award-info":[{"award-number":["BIF04"]}],"id":[{"id":"10.13039\/501100008454","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Georg Scheuing Stiftung","award":["NN"],"award-info":[{"award-number":["NN"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG Schu 646\/17-1"],"award-info":[{"award-number":["DFG Schu 646\/17-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG Schu 646\/20-1"],"award-info":[{"award-number":["DFG Schu 646\/20-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB TR128"],"award-info":[{"award-number":["SFB TR128"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SPP1656"],"award-info":[{"award-number":["SPP1656"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Leibniz Foundation","award":["SAW-2016-DFA-2"],"award-info":[{"award-number":["SAW-2016-DFA-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms21176288","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T08:11:19Z","timestamp":1598861479000},"page":"6288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Dietary Wheat Amylase Trypsin Inhibitors Impact Alzheimer\u2019s Disease Pathology in 5xFAD Model Mice"],"prefix":"10.3390","volume":"21","author":[{"given":"Malena","family":"dos Santos Guilherme","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center Johannes Gutenberg-University, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3135-1359","authenticated-orcid":false,"given":"Victor F.","family":"Zevallos","sequence":"additional","affiliation":[{"name":"Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center, 55131 Mainz, Germany"},{"name":"Nutrition and Food Research Group, Department of Applied and Health Sciences, University of Northumbria, Newcastle Upon Tyne NE1 8ST, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4463-9079","authenticated-orcid":false,"given":"Aline","family":"Pesi","sequence":"additional","affiliation":[{"name":"Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolai M.","family":"Stoye","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center Johannes Gutenberg-University, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vu Thu Thuy","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center Johannes Gutenberg-University, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantin","family":"Radyushkin","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Resilience Research, 55122 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2876-2352","authenticated-orcid":false,"given":"Andreas","family":"Schwiertz","sequence":"additional","affiliation":[{"name":"Institute of Microecology, 35745 Herborn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Resilience Research, 55122 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Detlef","family":"Schuppan","sequence":"additional","affiliation":[{"name":"Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center, 55131 Mainz, Germany"},{"name":"Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Endres","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center Johannes Gutenberg-University, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/joim.12959","article-title":"Current and emerging avenues for Alzheimer\u2019s disease drug targets","volume":"286","author":"Kenigsberg","year":"2019","journal-title":"J. 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