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
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.
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.
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.
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.
KeywordsGerm-free NOD mice Human gut microbiome transfer Type 1 diabetes
Inguinal lymph node
Mesenteric lymph node
Mixed-meal tolerance test
Pancreatic lymph node
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.
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.
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.
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