Microbiota-dependent proteolysis of gluten subverts diet-mediated protection against type 1 diabetes
Research output: Contribution to journal › Journal article › Research › peer-review
Diet and commensals can affect the development of autoimmune diseases like type 1 diabetes (T1D). However, whether dietary interventions are microbe-mediated was unclear. We found that a diet based on hydrolyzed casein (HC) as a protein source protects non-obese diabetic (NOD) mice in conventional and germ-free (GF) conditions via improvement in the physiology of insulin-producing cells to reduce autoimmune activation. The addition of gluten (a cereal protein complex associated with celiac disease) facilitates autoimmunity dependent on microbial proteolysis of gluten: T1D develops in GF animals monocolonized with Enterococcus faecalis harboring secreted gluten-digesting proteases but not in mice colonized with protease deficient bacteria. Gluten digestion by E. faecalis generates T cell-activating peptides and promotes innate immunity by enhancing macrophage reactivity to lipopolysaccharide (LPS). Gnotobiotic NOD Toll4-negative mice monocolonized with E. faecalis on an HC + gluten diet are resistant to T1D. These findings provide insights into strategies to develop dietary interventions to help protect humans against autoimmunity.
Original language | English |
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Journal | Cell Host and Microbe |
Volume | 31 |
Issue number | 2 |
Pages (from-to) | 213-227.e9 |
ISSN | 1931-3128 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Publisher Copyright:
© 2022 Elsevier Inc.
- celiac disease, diet and autoimmunity, insulin secretion regulation, microbial proteolysis of gluten, microbiota and autoimmunity, type 1 diabetes
Research areas
ID: 337601068