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Diabetologia

, Volume 62, Issue 7, pp 1291–1296 | Cite as

Human gut microbiota transferred to germ-free NOD mice modulate the progression towards type 1 diabetes regardless of the pace of beta cell function loss in the donor

  • Vit NeumanEmail author
  • Ondrej Cinek
  • David P. Funda
  • Tomas Hudcovic
  • Jaroslav Golias
  • Lenka Kramna
  • Lenka Petruzelkova
  • Stepanka Pruhova
  • Zdenek Sumnik
Short Communication

Abstract

Aims/hypothesis

This study aimed to assess the ability of human gut microbiota to delay the onset of type 1 diabetes when transferred into germ-free NOD mice.

Methods

Two children with rapid and three children with slow beta cell function loss (as assessed by C-peptide AUC change in the mixed-meal tolerance tests performed 1 and 12 months after type 1 diabetes onset), participating in an ongoing trial with gluten-free diet, donated faeces, which were transferred into germ-free NOD mice. The mice were subsequently followed for diabetes incidence.

Results

The bacterial profiles of bacteriome-humanised mice had significantly (p < 10−5) lower alpha diversity than the donor material, with marked shifts in ratios between the main phyla. Diabetes onset was significantly delayed in all bacteriome-humanised colonies vs germ-free NOD mice, but the pace of beta cell loss was not transferable to the mouse model.

Conclusions/interpretation

Germ-free NOD mice colonised with human gut microbiome are able to adopt a large proportion of transferred bacterial content, although the ratios of main phyla are reproduced only suboptimally. The recipient mice did not replicate the phenotype of the stool donor in relation to the pace towards type 1 diabetes.

Trial registration

ClinicalTrials.gov NCT02867436

Keywords

Germ-free NOD mice Human gut microbiome transfer Type 1 diabetes 

Abbreviations

ILN

Inguinal lymph node

MLN

Mesenteric lymph node

MMTT

Mixed-meal tolerance test

PLN

Pancreatic lymph node

Treg

T-regulatory cell

Notes

Acknowledgements

The content of this paper was presented at the annual conferences of International Society for Pediatric and Adolescent Diabetes (ISPAD) 2017 and Immunology of Diabetes (IDS) 2018. Some data were presented as an abstract at the ISPAD meeting in 2017.

Contribution statement

VN acquired and analysed the data and drafted the manuscript. LK and JG participated in the data analysis and critically revised the article. TH, LP and SP helped with the data acquisition and critically revised the manuscript. DF, ZS and OC have substantially contributed to the design of the study and revised the article. All co-authors were given the final version of the manuscript and approved its content. OC is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Funding

This study received funding from the Ministry of Health of the Czech Republic (AZV grant 16-27994A).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2019_4869_MOESM1_ESM.pdf (370 kb)
ESM Figures (PDF 369 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pediatrics, 2nd Faculty of MedicineCharles University and University Hospital MotolPrague 5Czech Republic
  2. 2.Institute of Microbiology of the Czech Academy of Sciences, v.v.i.Prague and Novy HradekCzech Republic

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