Vit Neuman1, Ondrej Cinek2, David P Funda3, Tomas Hudcovic3, Jaroslav Golias3, Lenka Kramna2, Lenka Petruzelkova2, Stepanka Pruhova2, Zdenek Sumnik2. 1. Department of Pediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Úvalu 84, CZ-15006, Prague 5, Czech Republic. Vit.Neuman@fnmotol.cz. 2. Department of Pediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Úvalu 84, CZ-15006, Prague 5, Czech Republic. 3. Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Prague and Novy Hradek, Czech Republic.
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.
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 NODmice. 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 NODmice. 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 NODmice, but the pace of beta cell loss was not transferable to the mouse model. CONCLUSIONS/ INTERPRETATION: Germ-free NODmice colonised with humangut 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.
Entities:
Keywords:
Germ-free NOD mice; Human gut microbiome transfer; Type 1 diabetes
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