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Innate immunity and intestinal microbiota in the development of Type 1 diabetes

Author

Listed:
  • Li Wen

    (Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA)

  • Ruth E. Ley

    (Center for Genome Sciences, Washington University School of Medicine, St Louis, Missouri 63108, USA
    Present address: Department of Microbiology, Cornell University, Ithaca, New York 14850, USA.)

  • Pavel Yu. Volchkov

    (University of Chicago, Chicago, Illinois 60637, USA)

  • Peter B. Stranges

    (University of Chicago, Chicago, Illinois 60637, USA
    The Jackson Laboratory, Bar Harbor, Maine 04609, USA)

  • Lia Avanesyan

    (University of Chicago, Chicago, Illinois 60637, USA
    The Jackson Laboratory, Bar Harbor, Maine 04609, USA)

  • Austin C. Stonebraker

    (The Jackson Laboratory, Bar Harbor, Maine 04609, USA)

  • Changyun Hu

    (Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA)

  • F. Susan Wong

    (School of Medical Science, Bristol University, Bristol, BS8 1TD, UK)

  • Gregory L. Szot

    (Diabetes Center at the University of California San Francisco, San Francisco, California 94143, USA)

  • Jeffrey A. Bluestone

    (Diabetes Center at the University of California San Francisco, San Francisco, California 94143, USA)

  • Jeffrey I. Gordon

    (Center for Genome Sciences, Washington University School of Medicine, St Louis, Missouri 63108, USA)

  • Alexander V. Chervonsky

    (University of Chicago, Chicago, Illinois 60637, USA
    The Jackson Laboratory, Bar Harbor, Maine 04609, USA)

Abstract

Microbes to counter diabetes The incidence of autoimmune diabetes in NOD (non-obese diabetic) mice, a lab model for type 1 diabetes, varies depending on the conditions in which they are kept. In particular, NOD mice exposed to killed mycobacteria and other microbial products are protected against the development of diabetes, suggesting the involvement of the rapid innate immune response. Experiments in NOD mice deficient in innate immunity — through the absence of the Toll-like receptor signal adaptor protein MyD88 — now show that both innate immunity and intestinal microbiota influence predisposition to diabetes. Germ-free MyD88-negative mice developed robust diabetes, yet in mice with a complement of gut microbes similar to the normal human gut, diabetes was reduced. This raises the prospect that live 'friendly' microbes, or microbial products might be therapeutic options for type 1 diabetes.

Suggested Citation

  • Li Wen & Ruth E. Ley & Pavel Yu. Volchkov & Peter B. Stranges & Lia Avanesyan & Austin C. Stonebraker & Changyun Hu & F. Susan Wong & Gregory L. Szot & Jeffrey A. Bluestone & Jeffrey I. Gordon & Alexa, 2008. "Innate immunity and intestinal microbiota in the development of Type 1 diabetes," Nature, Nature, vol. 455(7216), pages 1109-1113, October.
    • Handle: RePEc:nat:nature:v:455:y:2008:i:7216:d:10.1038_nature07336
    DOI: 10.1038/nature07336
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    Cited by:

    1. Javier A Carrero & Boris Calderon & Fadi Towfic & Maxim N Artyomov & Emil R Unanue, 2013. "Defining the Transcriptional and Cellular Landscape of Type 1 Diabetes in the NOD Mouse," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-14, March.
    2. Xiaoxiao Yuan & Ruirui Wang & Bing Han & ChengJun Sun & Ruimin Chen & Haiyan Wei & Linqi Chen & Hongwei Du & Guimei Li & Yu Yang & Xiaojuan Chen & Lanwei Cui & Zhenran Xu & Junfen Fu & Jin Wu & Wei Gu, 2022. "Functional and metabolic alterations of gut microbiota in children with new-onset type 1 diabetes," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Dongyang Yang & Wei Xu, 2023. "Estimation of Mediation Effect on Zero-Inflated Microbiome Mediators," Mathematics, MDPI, vol. 11(13), pages 1-16, June.
    4. Marko Sysi-Aho & Andrey Ermolov & Peddinti V Gopalacharyulu & Abhishek Tripathi & Tuulikki Seppänen-Laakso & Johanna Maukonen & Ismo Mattila & Suvi T Ruohonen & Laura Vähätalo & Laxman Yetukuri & Tain, 2011. "Metabolic Regulation in Progression to Autoimmune Diabetes," PLOS Computational Biology, Public Library of Science, vol. 7(10), pages 1-16, October.
    5. Estela Rosell-Mases & Alba Santiago & Marta Corral-Pujol & Francisca Yáñez & Encarna Varela & Leire Egia-Mendikute & Berta Arpa & Catalina Cosovanu & Anaïs Panosa & Gerard Serrano-Gómez & Conchi Mora , 2023. "Mutual modulation of gut microbiota and the immune system in type 1 diabetes models," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Abigail Nieves Delgado & Jan Baedke, 2021. "Does the human microbiome tell us something about race?," Palgrave Communications, Palgrave Macmillan, vol. 8(1), pages 1-12, December.
    7. Jean Lee & Leonid A. Yurkovetskiy & Derek Reiman & Lara Frommer & Zoe Strong & Anthony Chang & George J. Kahaly & Aly A. Khan & Alexander V. Chervonsky, 2024. "Androgens contribute to sex bias of autoimmunity in mice by T cell-intrinsic regulation of Ptpn22 phosphatase expression," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    8. Shinji Fukuda & Yumiko Nakanishi & Eisuke Chikayama & Hiroshi Ohno & Tsuneo Hino & Jun Kikuchi, 2009. "Evaluation and Characterization of Bacterial Metabolic Dynamics with a Novel Profiling Technique, Real-Time Metabolotyping," PLOS ONE, Public Library of Science, vol. 4(3), pages 1-10, March.

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