Wheat Consumption Aggravates Colitis in Mice via Amylase Trypsin Inhibitor–mediated Dysbiosis
| Autor: | Luisa Klotz, M. Ashfaq-Khan, Stefan Wirtz, Gui-Wei He, Geethanjali Pickert, Rambabu Surabattula, Detlef Schuppan, Rosario Heck, Ernesto Bockamp, Sebastian Rosigkeit, Christoph Becker, Friedrich Foerster, Andreas Weigert, Johannes Matzner, Julia-Stefanie Frick, Jan Wehkamp, M. Aslam, Dirk Ehmann, Dorothe Thies |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Trypsin inhibitor Plant Proteins Dietary Severity of Illness Index Inflammatory bowel disease Microbiology Feces Mice medicine Animals Humans Amylase Colitis Triticum Mice Knockout Hepatology biology Dextran Sulfate Gastroenterology food and beverages Fecal Microbiota Transplantation Inflammatory Bowel Diseases medicine.disease Animal Feed Immunity Innate Gastrointestinal Microbiome Toll-Like Receptor 4 Transplantation Disease Models Animal biology.protein TLR4 Dysbiosis Trypsin Inhibitors Signal Transduction |
| Zdroj: | Gastroenterology. 159:257-272.e17 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/j.gastro.2020.03.064 |
| Popis: | Background & Aims Wheat has become the world's major staple and its consumption correlates with prevalence of noncommunicable disorders such as inflammatory bowel diseases. Amylase trypsin inhibitors (ATIs), a component of wheat, activate the intestine's innate immune response via toll-like receptor 4 (TLR4). We investigated the effects of wheat and ATIs on severity of colitis and fecal microbiota in mice. Methods C57BL/6 wild-type and Tlr4–/– mice were fed wheat- or ATI-containing diets or a wheat-free (control) diet and then given dextran sodium sulfate to induce colitis; we also studied Il10–/– mice, which develop spontaneous colitis. Changes in fecal bacteria were assessed by taxa-specific quantitative polymerase chain reaction and 16S ribosomal RNA metagenomic sequencing. Feces were collected from mice on wheat-containing, ATI-containing, control diets and transplanted to intestines of mice with and without colitis on control or on ATI-containing diets. Intestinal tissues were collected and analyzed by histology, immunohistochemistry, and flow cytometry. Bacteria with reported immunomodulatory effects were incubated with ATIs and analyzed in radial diffusion assays. Results The wheat- or ATI-containing diets equally increased inflammation in intestinal tissues of C57BL/6 mice with colitis, compared with mice on control diets. The ATI-containing diet promoted expansion of taxa associated with development of colitis comparable to the wheat-containing diet. ATIs inhibited proliferation of specific human commensal bacteria in radial diffusion assays. Transplantation of microbiota from feces of mice fed the wheat- or ATI-containing diets to intestines of mice on control diets increased the severity of colitis in these mice. The ATI-containing diet did not increase the severity of colitis in Tlr4–/– mice. Conclusions Consumption of wheat or wheat ATIs increases intestinal inflammation in mice with colitis, via TLR4, and alters their fecal microbiota. Wheat-based, ATI-containing diets therefore activate TLR4 signaling and promote intestinal dysbiosis. |
| Databáze: | OpenAIRE |
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