116C-NOD GUT MICROBIOTA MODULATES TH RESPONSE AND AUTOIMMUNE DIABETES INCIDENCE OF NOD MICE
- Estela Rosell-Mases, Spain
Abstract
Background and Aims
The association between gut microbiota alterations and beta cell autoimmunity in type 1 diabetes (T1D) has been suggested by both animal model experiments and clinical studies. However, the adaptive immune system modulation exerted by the gut microbiota in the context of T1D remains poorly understood. To explore this issue, the islet beta cell-autoreactive B lymphocyte transgenic 116C-NOD mouse model, which surprisingly displays a decreased T1D incidence compared with NOD mouse, was used. Our objective was to analyze the effect of the 116C-NOD gut microbiota natural transfer on the immune phenotype, the intestinal microbial composition, and the progress of T1D in recipient NOD mice.
Methods
To achieve this goal, NOD mice were kept in isolation (isoNOD) or cohousing (coNOD) conditions regarding their transgenic 116C-NOD siblings. Fecal microbiome composition was analyzed using 16S rRNA gene sequencing. Immunological studies included B and T cell cytokine secretion profiling and population characterization after culture. T1D development was monitored by measuring glycosuria and glycaemia.
Results
Microbiome analysis revealed that coNOD harboured a different microbial profile compared with isoNOD mice. As for their immune phenotype, lymphocytes from coNOD mice developed a Th1/Th17 response, intermediate between the predominant Th1 pattern of isoNOD and the prevalent Th17 profile of 116C-NOD model. Furthermore, coNOD mice showed a significantly lower disease incidence than their isoNOD counterparts.
Conclusions
Taken together, these results suggest that 116C-NOD gut microbiota, previously tuned by the own 116C-NOD lymphocyte repertoire, may modify T1D development of recipient NOD mice through a Th status shift.