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The role of the intestinal microbiota in type 1 diabetes mellitus

Key Points

  • The disease process leading to type 1 diabetes mellitus (T1DM) is, in many cases, initiated during the first few years of life, when the intestinal microbiota undergoes dynamic development

  • The available data are insufficient to assess whether alterations in the gut microbiota are involved in the initiation of T1DM

  • After the appearance of the first disease-predictive autoantibodies, children who progress to clinical T1DM have a reduced bacterial diversity and a decreased abundance of bacteria that produce butyrate or lactate

  • The mechanisms by which intestinal microorganisms might affect the initiation of β-cell autoimmunity and the progression from seroconversion to clinical disease need to be identified

  • Standard operating procedures should be applied for the sampling, handling and storage of stool samples, as well as for DNA extraction, to minimize the effect of technical biases

Abstract

Type 1 diabetes mellitus (T1DM) is a chronic immune-mediated disease with a subclinical prodromal period, characterized by selective loss of insulin-producing-β cells in the pancreatic islets of genetically susceptible individuals. The incidence of T1DM has increased several fold in most developed countries since World War II, in conjunction with other immune-mediated diseases. Rapid environmental changes and modern lifestyles are probably the driving factors that underlie this increase. These effects might be mediated by changes in the human microbiota, particularly the intestinal microbiota. Research on the gut microbiome of individuals at risk of developing T1DM and in patients with established disease is still in its infancy, but initial findings indicate that the intestinal microbiome of individuals with prediabetes or diabetes mellitus is different to that of healthy individuals. The gut microbiota in individuals with preclinical T1DM is characterized by Bacteroidetes dominating at the phylum level, a dearth of butyrate-producing bacteria, reduced bacterial and functional diversity and low community stability. However, these changes seem to emerge after the appearance of autoantibodies that are predictive of T1DM, which suggests that the intestinal microbiota might be involved in the progression from β-cell autoimmunity to clinical disease rather than in the initiation of the disease process.

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Figure 1: Microbial community diversity and subsequent T1DM diagnosis.
Figure 2: Gut microbial gene content and development of T1DM.

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Acknowledgements

M.K. and H.S. acknowledge support from the Finnish Centre of Excellence in Molecular Systems Immunology and Physiology Research 2012–17 (Academy of Finland, Decision No. 250114).

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M.K. and H.S. researched data for the article, provided substantial contributions to the discussion of content, wrote the manuscript and reviewed and/or edited the manuscript before submission.

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Correspondence to Mikael Knip.

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Knip, M., Siljander, H. The role of the intestinal microbiota in type 1 diabetes mellitus. Nat Rev Endocrinol 12, 154–167 (2016). https://doi.org/10.1038/nrendo.2015.218

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