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

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-03-07 DOI:10.1126/science.adn0953

Jennifer Hampton Hill, Rickesha Bell, Logan Barrios, Halli Baird, Kyla Ost, Morgan Greenewood, Josh K 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

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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.

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新生真菌通过巨噬细胞依赖的β细胞发育促进终身代谢健康。

早期生命微生物多样性的丧失与糖尿病有关，但微生物影响疾病的机制仍然难以捉摸。我们在小鼠中报道了一个关键的新生儿窗口，当微生物群破坏导致β细胞发育减少导致终身代谢后果时。我们展示了人类中存在类似程序的证据，并确定了足以促进β细胞生长的特定真菌和细菌。微生物群在胰岛巨噬细胞的生长中也起着重要作用，发育过程中巨噬细胞的消耗会减少β细胞。念珠菌dubliniensis通过独特的细胞壁组成以巨噬细胞依赖的方式增加β细胞，并降低小鼠糖尿病发病率。β细胞消融或抗生素治疗后给予C. dubliniensis可改善β细胞功能。这些数据表明，真菌是促进长期代谢健康的关键早期共生生物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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