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

• 成果类型: Article
• 署名作者: Hill, Jennifer Hampton; Bell, Rickesha; Barrios, Logan; Baird, Halli; Ost, Kyla; Greenewood, Morgan; Monts, Josh K.; Tracy, Erin; Meili, Casey H.; Chiaro, Tyson R.; Weis, Allison M.; Guillemin, Karen; Beaudin, Anna E.; Murtaugh, L. Charles; Stephens, W. Zac; Round, June L.
• 署名单位: Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; University of Oregon; Canadian Institute for Advanced Research (CIFAR); Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13384
• DOI: 10.1126/science.adn0953
• 发表日期: 2025-03-07
• 关键词: gut microbiome; resident macrophages; pancreatic-islets; primary mechanism; replication; population; repressor; nrg1; mass

摘要

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 beta cell development. We show evidence for the existence of a similar program in humans and identify specific fungi and bacteria that are sufficient for beta cell growth. The microbiota also plays an important role in seeding islet-resident macrophages, and macrophage depletion during development reduces beta cells. Candida dubliniensis increases beta cells in a macrophage-dependent manner through distinctive cell wall composition and reduces murine diabetes incidence. Provision of C. dubliniensis after beta cell ablation or antibiotic treatment improves beta cell function. These data identify fungi as critical early-life commensals that promote long-term metabolic health.