Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous XXXX model of autoimmune insulin-dependent diabetes.

@entity1 @entity2176 @entity3273 @entity6 @entity19 @entity6636 @entity3639 @entity1961 @entity869 @entity636 @entity526
Insulin-dependent or type 1 @entity6 is a prototypic autoimmune disease whose incidence steadily increased over the past decades in industrialized countries. Recent evidence suggests the importance of the gut microbiota to explain this trend. Here, non-obese @entity6 (NOD) @entity19 that spontaneously develop autoimmune type 1 @entity6 were treated with different antibiotics to explore the influence of a targeted @entity6636 in the progression of the disease. A mixture of wide spectrum antibiotics (i.e. @entity3639 , @entity3273 and @entity869 ) or @entity2176 alone were administered orally from the moment of conception, treating breeding pairs, and during the postnatal and adult life until the end of follow-up at 40 weeks. @entity6 significantly and similarly increased in male @entity19 following treatment with these two antibiotic regimens. In NOD females a slight yet not significant trend towards an increase in disease incidence was observed. Changes in gut microbiota composition were assessed by sequencing the V3 region of bacterial 16S rRNA genes. Administration of the antibiotic mixture resulted in near complete ablation of the gut microbiota. @entity2176 treatment led to increased @entity526 , Lactobacillus and Sutterella genera and decreased members of the Clostridiales order and Lachnospiraceae, Prevotellaceae and Rikenellaceae families, as compared to control @entity19 . Massive elimination of @entity636 -producing cells, both @entity1961 +TCRab+ and TCRy  + T cells was observed in the lamina propria of the ileum and the colon of @entity2176 -treated @entity19 . These results show that a directed even partial ablation of the gut microbiota, as induced by @entity2176 , significantly increases type 1 @entity6 incidence in male NOD @entity19 thus prompting for caution in the use of antibiotics in pregnant @entity1 and newborns.
