Neonatal fungi promote lifelong metabolic health through macrophage-dependent β cell development
Jennifer Hampton Hill, Rickesha Bell, Logan Barrios, Halli Baird, Kyla S. Ost, Morgan Greenewood, Josh Monts, Erin Tracy, Casey H. Meili, Tyson R. Chiaro, Allison M. Weis, Karen Guillemin, Anna E. Beaudin, L. Charles Murtaugh, W. Zac Stephens, June L. Round
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.