Neonatal fungi promote lifelong metabolic health through macrophage-dependent β cell development

Abstract

Loss of early-life microbial diversity is correlated with diabetes, yet mechanisms by which microbes influence disease remain elusive. We report a critical neonatal window in mice when microbiota disruption results in lifelong metabolic consequences stemming from reduced β cell development. We show evidence for the existence of a similar program in humans and identify specific fungi and bacteria that are sufficient for β cell growth. The microbiota also plays an important role in seeding islet-resident macrophages, and macrophage depletion during development reduces β cells. Candida dubliniensis increases β cells in a macrophage-dependent manner through distinctive cell wall composition and reduces murine diabetes incidence. Provision of C. dubliniensis after β cell ablation or antibiotic treatment improves β cell function. These data identify fungi as critical early-life commensals that promote long-term metabolic health.