Lactobacilli Degrade Wheat Amylase Trypsin Inhibitors to Reduce Intestinal Dysfunction Induced by Immunogenic Wheat Proteins
Open accessAbstract
Background & aims Wheat-related disorders, a spectrum of conditions induced by the ingestion of gluten-containing cereals, have been increasing in prevalence. Patients with celiac disease have gluten-specific immune responses, but the contribution of non-gluten proteins to symptoms in patients with celiac disease or other wheat-related disorders is controversial.Methods C57BL/6 (control), Myd88-/-, Ticam1-/-, and Il15-/- mice were placed on diets that lacked wheat or gluten, with or without wheat amylase trypsin inhibitors (ATIs), for 1 week. Small intestine tissues were collected and intestinal intraepithelial lymphocytes (IELs) were measured; we also investigated gut permeability and intestinal transit. Control mice fed ATIs for 1 week were gavaged daily with Lactobacillus strains that had high or low ATI-degrading capacity. Nonobese diabetic/DQ8 mice were sensitized to gluten and fed an ATI diet, a gluten-containing diet or a diet with ATIs and gluten for 2 weeks. Mice were also treated with Lactobacillus strains that had high or low ATI-degrading capacity. Intestinal tissues were collected and IELs, gene expression, gut permeability and intestinal microbiota profiles were measured.Results In intestinal tissues from control mice, ATIs induced an innate immune response by activation of Toll-like receptor 4 signaling to MD2 and CD14, and caused barrier dysfunction in the absence of mucosal damage. Administration of ATIs to gluten-sensitized mice expressing HLA-DQ8 increased intestinal inflammation in response to gluten in the diet. We found ATIs to be degraded by Lactobacillus, which reduced the inflammatory effects of ATIs.Conclusions ATIs mediate wheat-induced intestinal dysfunction in wild-type mice and exacerbate inflammation to gluten in susceptible mice. Microbiome-modulating strategies, such as administration of bacteria with ATI-degrading capacity, may be effective in patients with wheat-sensitive disorders.
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Gut microbial proteases are able to digest wheat amylase trypsin inhibitors, thereby reducing the intestinal dysfunction associated with wheat proteins.
“Gut microbial proteases are able to digest ATI, thereby reducing the intestinal dysfunction associated with wheat proteins.101”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [101]
Lactobacillus strains degrade both gluten and wheat amylase trypsin inhibitor peptides, reducing their immunogenic properties.
“For example, Lactobacillus strains degrade both gluten and ATI peptides, reducing their immunogenic properties.18,101”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [101]
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Self-citation
- Authors
- Caminero, A., McCarville, J. L., Zevallos, V. F., Pigrau, M., Yu, X. B., Jury, J., Galipeau, H. J., Clarizio, A. V., Casqueiro, J., Murray, J. A., Collins, S. M., Alaedini, A., Bercik, P., Schuppan, D., & Verdu, E. F.
- Affiliations
- McMaster University (CA)
- Johannes Gutenberg University Mainz (DE)
- Columbia University Irving Medical Center (US)
- Universidad de León (ES)
- Mayo Clinic (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Verdu, Elena F.
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 156
- Issue
- 8
- Pages
- 2266-2280
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2915151993
- Cited by
- 136
- References
- 61
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 15 · 2023: 13 · 2022: 23 · 2021: 24 · 2020: 21 · 2019: 12
- FWCI
- 18.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- St Mary's University Repository (ULCC) (submittedVersion)
- Funders
- Canadian Institutes of Health Research (142773)
- Allegheny Technologies Incorporated
- Deutsche Forschungsgemeinschaft (Schu 646/17-1, Pic/Sch SPP 1656)
- National Institutes of Health
- Mayo Foundation for Medical Education and Research
- Canadian Celiac Association (US8617536)
- Topics
- Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- Lactobacillus, celiac disease, gluten sensitivity, intestinal barrier dysfunction, intestinal permeability, intraepithelial lymphocytes, TLR4 signaling, intestinal inflammation, HLA-DQ8, gut microbiota, probiotics
- MeSH terms
- Gastrointestinal Microbiome, Amylases, Animals, Celiac Disease, Disease Models, Animal, Gliadin, Humans, Immunity, Innate, Lactobacillus, Mice, Inbred C57BL, Random Allocation, Reference Values, Sensitivity and Specificity, Trypsin Inhibitors, Triticum, Mice, Diet, Gluten-Free
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