Neonatal fungi promote lifelong metabolic health through macrophage-dependent β cell development
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. <i>Candida dubliniensis</i> increases β cells in a macrophage-dependent manner through distinctive cell wall composition and reduces murine diabetes incidence. Provision of <i>C. dubliniensis</i> 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.
Authors
- Casey H. Meili (ORCID: https://orcid.org/0000-0003-0379-3440)
- Karen Guillemin (ORCID: https://orcid.org/0000-0001-6004-9955)
- Kyla S. Ost (ORCID: https://orcid.org/0000-0003-4101-2836)
- Erin Tracy (ORCID: https://orcid.org/0000-0001-6523-4156)
- Anna E. Beaudin (ORCID: https://orcid.org/0000-0002-8580-8660)
- Rickesha Bell (ORCID: https://orcid.org/0000-0002-0554-0730)
- Tyson R. Chiaro (ORCID: https://orcid.org/0000-0002-8132-5186)
- Josh Monts (ORCID: https://orcid.org/0000-0003-0100-8939)
- Jennifer Hampton Hill (ORCID: https://orcid.org/0000-0002-5544-1423)
- June L. Round (ORCID: https://orcid.org/0000-0002-7158-9874)
- Halli Baird
- L. Charles Murtaugh (ORCID: https://orcid.org/0000-0001-7353-4706)
- Allison M. Weis (ORCID: https://orcid.org/0000-0001-9991-1661)
- W. Zac Stephens (ORCID: https://orcid.org/0000-0002-8072-9023)
- Logan Barrios (ORCID: https://orcid.org/0000-0003-4033-6054)
- Morgan Greenewood
Institutions
- Canadian Institute for Advanced Research (CA)
- University of Oregon (US)
- University of Utah (US)
- University of Colorado Anschutz Medical Campus (US)
Publication Details
- Journal
- Science
- Published
- 2025-03-06
- DOI
- https://doi.org/10.1126/science.adn0953
- Citations
- 19
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 38.12
Funders
- W. M. Keck Foundation
- Leona M. and Harry B. Helmsley Charitable Trust
- National Institutes of Health
- Centers for Disease Control and Prevention
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Environmental Health Sciences
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development