NOD mice tag-encoded 454/FLX Titanium (Roche) pyro-sequencing of the V3 and V4 region of the 16S rRNA gene. Mus musculus

Delivery mode have long been associated with long-term changes in gut microbiota and more re-cently also with changes in the immune system. This has further been suggested to link C-section with an increased risk of developing immune-mediated diseases such as type 1 diabetes (T1D). However, lack of proper models makes it challenging to clarify. In this study we demonstrate that changing early life events by cesarean delivery and cross-fostering with genetically distinct strain both influence the gut microbiota composition in mice. 16S sequencing analysis revealed a distinct bacterial profile at weaning characterized by more abundant Bacteroides and Lachnospiraceae and less represented by Rikenellaceae and Ruminococcus. However, no clustering in principal compo-nent analysis was evident in adult mice older than 16 weeks of age. Furthermore, the adult mice born by cesarean section (C-section) had lower proportions of FoxP3+ regulatory T cells, tolerogen-ic CD103+ dendritic cells, and less Il10 gene expression in mesenteric lymph nodes and spleens. This demonstrates a long-term systemic effect on the regulatory immune system, also in the non-obese diabetic model of T1D; though no effect was seen on diabetes incidence or insulitis develop-ment. In conclusion, the first exposure to microorganisms seems to be crucial for the establishment of a gut microbiota and subsequent priming of regulatory immune system in mice; and mode of delivery strongly influences this, although the impact on the microbiota in some aspects is different from the impact observed in humans.