Gut microbiota and pathobiont exposure influences disease incidence in non-obese diabetic mice

While the non-obese diabetic (NOD) mouse is the most widely used animal model of type 1 diabetes (T1D), it suffers from poor reproducibility in disease incidence often attributed to variables in the environment, including the gut microbiota (GM). Prior research suggests a protective effect of segmented filamentous bacteria (SFB) on disease incidence, but it is unclear whether other pathobiont organisms or resident GM affect disease incidence. The objectives of the current study were to determine the effect of supplier-origin GMs and three different microbial challenges (SFB, Helicobacter hepaticus, and Mouse Hepatitis Virus [MHV]) on early-stage insulitis and lifelong disease incidence in NOD mice. The fecal microbiome was assessed pre- and post-disease onset to identify shifts in composition and predicted function of the GM. Results show that all three microbes influence T1D incidence and insulitis severity. Overall, SFB, MHV, and a high-richness microbiome were associated with lower disease incidence, while H. hepaticus and a low-richness microbiome were associated with higher disease incidence. H. hepaticus, but not SFB or MHV, was associated with significant changes in beta-diversity of the GM. While immune outcomes were not included, these findings provide guidance on microbes affecting disease incidence in NOD mice and evidence that such microbes may contribute to poor reproducibility in NOD mice or other mouse models.