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New therapeutic perspectives in Type 1 Diabetes: dietary interventions prevent β cell-autoimmunity by modifying the gut metabolic environment

Cellular & Molecular Immunology volume 14, pages 951–953 (2017)Cite this article

The gut microbiota plays a key role in the pathogenesis of autoimmune diseases such as Type 1 Diabetes (T1D), but the mechanism underlying this modulation is yet to be defined. This paper highlights the crucial role of the microbiota-induced gut metabolic profile, rather than the presence of single bacterial strains, in T1D modulation. Most importantly, it provides the first evidence that dietary interventions can modulate the autoimmune pathogenesis of T1D by altering the gut metabolic environment.

Substantial environmental changes and lifestyle modifications have been held responsible for the dramatic peak in the incidence of autoimmune diseases like T1D that occurred in the last half century in developed countries, the so-called ‘autoimmune epidemic’.1 Many environmental modifications such as changes in dietary habits, higher hygiene conditions and extensive use of antibiotics might have increased incidence of autoimmune diseases by altering the human intestinal microbiota. In fact, the gut microbiota has a strong impact in the immune system not only at the intestinal level but also systemically and modulate extra-intestinal autoimmune diseases like T1D.2 Effector T cells migrate from the gut to peripheral lymphoid organs and tissues3 and chronic inflammation and altered Teff/Treg cell ratio in the intestinal mucosa can underlie the pathogenesis of extra-intestinal autoimmune diseases like T1D as demonstrated in humans4 and pre-clinical models.5 Those lines of evidence support the notion that extra-intestinal autoimmune diseases and T1D can be prevented by promoting a beneficial gut microbiota profile and restoring a correct immune homeostasis at the intestinal level through administration of probiotics.6 However, it is now clear that it is not the presence of specific bacterial strains that modulates the immune system but rather the microbiota-associated metabolic pathways induced at the intestinal level by different microbial consortia. In a study performed in atopic children, immune dysregulation and allergy were associated with activation of microbial genes linked to specific metabolic pathways.7 For example, short chain fatty acids (SCFAs), that is, butyrate, propionate and acetate, are metabolites produced by bacterial communities that use xylane, xylose, and carboxymethylcellulose for their metabolism and are crucial to maintain gut barrier integrity8 and intestinal immune homeostasis.9 A SCFA-enriched gut metabolic environment promotes immune tolerance by enhancing FoxP3+ Treg cell expansion.10 This led to the hypothesis that a SCFA-enriched gut metabolic environment could prevent extra-intestinal autoimmune diseases like T1D by restoring immune tolerance at the intestinal and systemic level.

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Authors and Affiliations

  1. Department of Medicine, Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden

    Chiara Sorini

  2. Division of Immunology, Experimental Diabetes Unit-DRI, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Ilaria Cosorich & Marika Falcone

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  1. Chiara Sorini
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  2. Ilaria Cosorich
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  3. Marika Falcone
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Correspondence to Marika Falcone.

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Sorini, C., Cosorich, I. & Falcone, M. New therapeutic perspectives in Type 1 Diabetes: dietary interventions prevent β cell-autoimmunity by modifying the gut metabolic environment. Cell Mol Immunol 14, 951–953 (2017). https://doi.org/10.1038/cmi.2017.62

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