Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell-mediated 
destruction of the insulin-secreting pancreatic beta cells. During the past 50 
years T1D incidence has increased dramatically in many countries accompanied by 
an earlier age of onset especially in persons with lower genetic risk. These 
observations have prompted investigations of dynamic environmental factors that 
may contributor to risk for anti-pancreatic immunity. The gut and pancreas are 
anatomically and biochemically linked through the enteroinsular axis, a system 
in which gut-derived immune and metabolic signals have the potential to evoke 
effects in the pancreas. The gut microbiome (i.e. the 100 trillion symbiotic 
microorganisms which inhabit the mammalian gastrointestinal tract) influences 
numerous aspects of host metabolism, development and immunity. Here we examine 
recent evidence linking gut microbiome composition and function to pancreatic 
autoimmunity. Studies in children with genetic risk factors for T1D and analyses 
of the microbiome in rodent models have begun to associations between an altered 
microbiome composition potentially favoring a pro-inflammatory intestinal 
metabolic milieu and T1D. We discuss how environmental factors during critical 
developmental windows - gestation, birth, weaning and puberty may contribute to 
T1D risk. For example mode of delivery (vaginal or C-section) and exposure to 
antibiotics (pre- or post-natally) are two factors that modulate the maternal 
and/or offspring microbiome and can impact T1D development. Taken together, 
these emerging data underscore the requirement for longitudinal studies and 
mechanistic investigations in human subjects and rodent models to identify the 
basis for microbiome modulation of T1D and to identify biomarkers and 
therapeutics to improve the delayed onset and prevention of the disease.