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

Science. 2025 Mar 7;387(6738):eadn0953. doi: 10.1126/science.adn0953. Epub 2025 Mar 7.

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.

MeSH terms

  • Animals
  • Animals, Newborn
  • Candida* / physiology
  • Cell Wall / chemistry
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Insulin-Secreting Cells* / metabolism
  • Insulin-Secreting Cells* / microbiology
  • Insulin-Secreting Cells* / physiology
  • Macrophages* / immunology
  • Macrophages* / microbiology
  • Macrophages* / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD