Microbiota-dependent proteolysis of gluten subverts diet-mediated protection against type 1 diabetes

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Microbiota-dependent proteolysis of gluten subverts diet-mediated protection against type 1 diabetes. / Funsten, Matthew C.; Yurkovetskiy, Leonid A.; Kuznetsov, Andrey; Reiman, Derek; Hansen, Camilla H.F.; Senter, Katharine I.; Lee, Jean; Ratiu, Jeremy; Dahal-Koirala, Shiva; Antonopoulos, Dionysios A.; Dunny, Gary M.; Sollid, Ludvig M.; Serreze, David; Khan, Aly A.; Chervonsky, Alexander V.

In: Cell Host and Microbe, Vol. 31, No. 2, 2023, p. 213-227.e9.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Funsten, MC, Yurkovetskiy, LA, Kuznetsov, A, Reiman, D, Hansen, CHF, Senter, KI, Lee, J, Ratiu, J, Dahal-Koirala, S, Antonopoulos, DA, Dunny, GM, Sollid, LM, Serreze, D, Khan, AA & Chervonsky, AV 2023, 'Microbiota-dependent proteolysis of gluten subverts diet-mediated protection against type 1 diabetes', Cell Host and Microbe, vol. 31, no. 2, pp. 213-227.e9. https://doi.org/10.1016/j.chom.2022.12.009

APA

Funsten, M. C., Yurkovetskiy, L. A., Kuznetsov, A., Reiman, D., Hansen, C. H. F., Senter, K. I., Lee, J., Ratiu, J., Dahal-Koirala, S., Antonopoulos, D. A., Dunny, G. M., Sollid, L. M., Serreze, D., Khan, A. A., & Chervonsky, A. V. (2023). Microbiota-dependent proteolysis of gluten subverts diet-mediated protection against type 1 diabetes. Cell Host and Microbe, 31(2), 213-227.e9. https://doi.org/10.1016/j.chom.2022.12.009

Vancouver

Funsten MC, Yurkovetskiy LA, Kuznetsov A, Reiman D, Hansen CHF, Senter KI et al. Microbiota-dependent proteolysis of gluten subverts diet-mediated protection against type 1 diabetes. Cell Host and Microbe. 2023;31(2):213-227.e9. https://doi.org/10.1016/j.chom.2022.12.009

Author

Funsten, Matthew C. ; Yurkovetskiy, Leonid A. ; Kuznetsov, Andrey ; Reiman, Derek ; Hansen, Camilla H.F. ; Senter, Katharine I. ; Lee, Jean ; Ratiu, Jeremy ; Dahal-Koirala, Shiva ; Antonopoulos, Dionysios A. ; Dunny, Gary M. ; Sollid, Ludvig M. ; Serreze, David ; Khan, Aly A. ; Chervonsky, Alexander V. / Microbiota-dependent proteolysis of gluten subverts diet-mediated protection against type 1 diabetes. In: Cell Host and Microbe. 2023 ; Vol. 31, No. 2. pp. 213-227.e9.

Bibtex

@article{d47c54c8e3844429aa797c77f488e83c,
title = "Microbiota-dependent proteolysis of gluten subverts diet-mediated protection against type 1 diabetes",
abstract = "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.",
keywords = "celiac disease, diet and autoimmunity, insulin secretion regulation, microbial proteolysis of gluten, microbiota and autoimmunity, type 1 diabetes",
author = "Funsten, {Matthew C.} and Yurkovetskiy, {Leonid A.} and Andrey Kuznetsov and Derek Reiman and Hansen, {Camilla H.F.} and Senter, {Katharine I.} and Jean Lee and Jeremy Ratiu and Shiva Dahal-Koirala and Antonopoulos, {Dionysios A.} and Dunny, {Gary M.} and Sollid, {Ludvig M.} and David Serreze and Khan, {Aly A.} and Chervonsky, {Alexander V.}",
note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2023",
doi = "10.1016/j.chom.2022.12.009",
language = "English",
volume = "31",
pages = "213--227.e9",
journal = "Cell Host & Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - Microbiota-dependent proteolysis of gluten subverts diet-mediated protection against type 1 diabetes

AU - Funsten, Matthew C.

AU - Yurkovetskiy, Leonid A.

AU - Kuznetsov, Andrey

AU - Reiman, Derek

AU - Hansen, Camilla H.F.

AU - Senter, Katharine I.

AU - Lee, Jean

AU - Ratiu, Jeremy

AU - Dahal-Koirala, Shiva

AU - Antonopoulos, Dionysios A.

AU - Dunny, Gary M.

AU - Sollid, Ludvig M.

AU - Serreze, David

AU - Khan, Aly A.

AU - Chervonsky, Alexander V.

N1 - Publisher Copyright: © 2022 Elsevier Inc.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - celiac disease

KW - diet and autoimmunity

KW - insulin secretion regulation

KW - microbial proteolysis of gluten

KW - microbiota and autoimmunity

KW - type 1 diabetes

U2 - 10.1016/j.chom.2022.12.009

DO - 10.1016/j.chom.2022.12.009

M3 - Journal article

C2 - 36603588

AN - SCOPUS:85147344238

VL - 31

SP - 213-227.e9

JO - Cell Host & Microbe

JF - Cell Host & Microbe

SN - 1931-3128

IS - 2

ER -

ID: 337601068