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

Jennifer Hampton Hill1, Rickesha Bell1, Logan Barrios1

  • 1Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, UT, USA.

Science (New York, N.Y.)
|March 6, 2025
PubMed

Insights

Early-life gut microbes are crucial for metabolic health. Disrupting microbial diversity in newborns can lead to lifelong diabetes risk by impairing pancreatic beta cell development, with specific fungi like Candida dubliniensis showing protective effects.

Area of Science:

  • Microbiology
  • Immunology
  • Metabolic Diseases

Background:

  • Loss of early-life microbial diversity is linked to diabetes.
  • Mechanisms connecting gut microbes to metabolic disease are not fully understood.

Purpose of the Study:

  • Investigate the role of early-life microbiota in metabolic health.
  • Identify specific microbes influencing pancreatic beta cell development and function.
  • Explore the interplay between microbiota, macrophages, and beta cells.

Main Methods:

  • Neonatal microbiota disruption in mice.
  • Analysis of beta cell development and function.
  • Macrophage depletion studies.
  • Human cohort analysis.
  • Fungal and bacterial administration studies.

Main Results:

  • Neonatal microbiota disruption causes lifelong metabolic dysfunction due to reduced beta cell development in mice.
  • A similar phenomenon was observed in humans.
  • Specific fungi and bacteria were identified as sufficient for beta cell growth.
  • The microbiota influences islet-resident macrophages, which are critical for beta cell numbers.
  • Candida dubliniensis promotes beta cell expansion in a macrophage-dependent manner and reduces diabetes incidence in mice.
  • C. dubliniensis administration improved beta cell function post-ablation or antibiotic treatment.

Conclusions:

  • Fungi are critical early-life commensals that promote long-term metabolic health.
  • Targeting specific microbes, like C. dubliniensis, may offer therapeutic strategies for metabolic diseases.

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