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Gut microbiota metabolites for sweetening type I diabetes

Cellular & Molecular Immunology volume 15, pages 92–95 (2018)Cite this article

Type 1 diabetes (T1D), also referred to as insulin-dependent diabetes mellitus, is a debilitating disease that follows the destruction of pancreatic insulin-producing β cells by autologous T-cells. T1D primarily affects children and has a strong genetic component, with >50 susceptibility loci identified, including HLA-DQβ chains.1 However, the striking differences between European regions with similar genetic backgrounds and a sharp rise in T1D incidence in developed countries over the last several decades suggest that environmental factor(s) also play a relevant etiopathogenic role.2 Given the accumulating evidence linking the gut microbiota to protection against metabolic diseases,3 Mariño et al.4 recently tested the hypothesis that short-chain fatty acids (SCFAs), which are the end products of fermentation of dietary fibers by anaerobic intestinal microbiota, can protect genetically susceptible mice from developing T1D. Interestingly, the authors found that diets enriched in acetate or butyrate (two of the main SCFAs) can protect animals from developing diabetes through different and complementary cellular mechanisms. Such findings significantly enhance our understanding of the role of diet and gut microbiota in the development of autoimmune diseases and indicate that the use of medicinal foods may be a cost-effective treatment against T1D and other autoimmune diseases with a cellular component. Given that current anti-T1D approaches (which focus on prevention or modulation of the adaptive specific immune response against autoantigens) have been generally disappointing,5 such a new and refreshing strategy has attracted a great deal of attention (reviewed in Ref. 2).

Over the last decade, an ever-growing body of evidence has established that the gut microbiota is one of the most important epigenetic determinants of prevalent metabolic disorders such as type 2 diabetes and metabolic syndrome.6 Similarly, accumulating experimental observations indicate that T1D incidence in non-obese diabetic (NOD) mice is influenced by the microbial environment, thus indicating that the gut microbiota is involved in T1D development.7 This concept has been well-illustrated by a recent report demonstrating that the interaction between the gut microbiota and the host immune system was essential for the prevention and treatment of T1D.8 In their study, Wen et al. generated myeloid differentiation primary response 88 (MyD88)-deficient mice in a NOD background (NOD.Myd88−/−). MyD88 is a master regulator of immune responses and is capable of detecting bacteria and other infectious agents by binding to Toll-like receptors and initiating a pro-inflammatory cascade dependent on nuclear factor kappa beta (NF-κB) activation. NOD.Myd88−/− mice kept under specific-pathogen free conditions were completely protected against T1D development, but this protection was dependent on commensal microbiota, as NOD.Myd88−/− mice housed in germ-free (GF) conditions developed robust diabetes. Importantly, when these animals were colonized with altered Schaedler’s flora, which is a consortium of six bacteria that are normally found in the human gut, protection against T1D was restored. Molecular analyses of cecal microbiota revealed that MyD88 ablation correlates with changes in the microbiota composition, with a significant increase in butyrate-producing Firmicutes, as well as Rikenellaceae and Porphoromadaceae.

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References

  1. Todd JA, Bell JI, McDevitt HO . HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 1987; 329: 599–604.

    Article  CAS  Google Scholar 

  2. Paun A, Yau C, Danska JS . The influence of the microbiome on Type 1 diabetes. J Immunol 2017; 198: 590–595.

    Article  CAS  Google Scholar 

  3. Shi Y, Mu L . An expanding stage for commensal microbes in host immune regulation. Cell Mol Immunol 2017; 14: 339–348.

    Article  CAS  Google Scholar 

  4. Marino E, Richards JL, McLeod KH, Stanley D, Yap YA, Knight J et al. Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat Immunol 2017; 18: 552–562.

    Article  CAS  Google Scholar 

  5. Kolb H, von Herrath M . Immunotherapy for Type 1 diabetes: why do current protocols not halt the underlying disease process? Cell Metab 2017; 25: 233–241.

    Article  CAS  Google Scholar 

  6. Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI . The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 2009; 1: 6ra14.

    Article  Google Scholar 

  7. Anderson MS, Bluestone JA . The NOD mouse: a model of immune dysregulation. Annu Rev Immunol 2005; 23: 447–485.

    Article  CAS  Google Scholar 

  8. Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 2008; 455: 1109–1113.

    Article  CAS  Google Scholar 

  9. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly YM et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013; 341: 569–573.

    Article  CAS  Google Scholar 

  10. Amrani A, Verdaguer J, Serra P, Tafuro S, Tan R, Santamaria P . Progression of autoimmune diabetes driven by avidity maturation of a T-cell population. Nature 2000; 406: 739–742.

    Article  CAS  Google Scholar 

  11. Marino E, Tan B, Binge L, Mackay CR, Grey ST . B-cell cross-presentation of autologous antigen precipitates diabetes. Diabetes 2012; 61: 2893–2905.

    Article  CAS  Google Scholar 

  12. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 2013; 504: 446–450.

    Article  CAS  Google Scholar 

  13. Takiishi T, Cook DP, Korf H, Sebastiani G, Mancarella F, Cunha JP et al. Reversal of diabetes in NOD mice by clinical-grade proinsulin and IL-10-secreting lactococcus lactis in combination with low- dose anti-CD3 depends on the induction of Foxp3-positive T cells. Diabetes 2017; 66: 448–459.

    Article  CAS  Google Scholar 

  14. Jayasinghe TN, Chiavaroli V, Holland DJ, Cutfield WS, O'Sullivan JM . The new era of treatment for obesity and metabolic disorders: evidence and expectations for gut microbiome transplantation. Front Cell Infect Microbiol 2016; 6: 15.

    Article  Google Scholar 

  15. Tai N, Wong FS, Wen L . The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Rev Endocr Metab Disord 2015; 16: 55–65.

    Article  CAS  Google Scholar 

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Acknowledgements

The work by FL is supported by grants from the Worldwide Cancer Research (14-1275), Fundació La Marató TV3 (201319-30), and Spanish Ministerio de Economía y Competitividad (Plan Nacional I+D+i, SAF2013-46151-R and SAF2016-80535-R) -co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF. FA holds Sara Borrell (CD15/00016) and M-AES (MV16/00002) fellowships from Instituto de Salud Carlos III. TA is supported by the Cultural Mission of the Royal Embassy of Saudi Arabia (Qassim University).

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  1. Thamer Aljutaily and Marta Consuegra-Fernández: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Health and Nutritional Sciences, South Dakota State University, Brookings, SD, USA

    Thamer Aljutaily & Eduardo Huarte

  2. Group of Immunoreceptors of the Innate and Adaptive System, Institute d’Investigacions Biomédiques August pi i Sunyer (IDIBAPS), Barcelona, Spain

    Marta Consuegra-Fernández, Fernando Aranda & Francisco Lozano

  3. Department of Immunology, Hospital Clínic of Barcelona, Barcelona, Spain

    Francisco Lozano

  4. Department de Biomedical Sciences, University of Barcelona, Barcelona, Spain

    Francisco Lozano

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  1. Thamer Aljutaily
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Correspondence to Francisco Lozano or Eduardo Huarte.

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Aljutaily, T., Consuegra-Fernández, M., Aranda, F. et al. Gut microbiota metabolites for sweetening type I diabetes. Cell Mol Immunol 15, 92–95 (2018). https://doi.org/10.1038/cmi.2017.65

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