| First Author | Funsten MC | Year | 2023 |
| Journal | Cell Host Microbe | Volume | 31 |
| Issue | 2 | Pages | 213-227.e9 |
| PubMed ID | 36603588 | Mgi Jnum | J:335286 |
| Mgi Id | MGI:7434050 | Doi | 10.1016/j.chom.2022.12.009 |
| Citation | Funsten MC, et al. (2023) Microbiota-dependent proteolysis of gluten subverts diet-mediated protection against type 1 diabetes. Cell Host Microbe 31(2):213-227.e9 |
| abstractText | 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. |
