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Early-life gut mycobiome core species modulate metabolic health in mice

Author

Listed:
  • Mackenzie W. Gutierrez

    (University of Calgary
    University of Calgary
    University of Calgary
    University of Calgary)

  • Erik van Tilburg Bernardes

    (University of Calgary
    University of Calgary
    University of Calgary
    University of Calgary)

  • Ellen Ren

    (University of Calgary
    University of Calgary
    University of Calgary
    University of Calgary)

  • Kristen N. Kalbfleisch

    (University of Calgary
    University of Calgary
    University of Calgary
    University of Calgary)

  • Madeline Day

    (University of Calgary
    University of Calgary
    University of Calgary
    University of Calgary)

  • Ewandson Luiz Lameu

    (University of Calgary
    University of Calgary)

  • Thaís Glatthardt

    (University of Calgary
    University of Calgary
    University of Calgary
    University of Calgary)

  • Emily M. Mercer

    (University of Calgary
    University of Calgary
    University of Calgary
    University of Calgary)

  • Sunita Sharma

    (University of Calgary
    University of Calgary
    University of Calgary
    University of Calgary)

  • Hong Zhang

    (University of Calgary
    University of Calgary)

  • Ali Al-Azawy

    (University of Calgary
    University of Calgary
    University of Calgary
    University of Calgary)

  • Faye Chleilat

    (University of Calgary
    Stanford University School of Medicine)

  • Simon A. Hirota

    (University of Calgary
    University of Calgary)

  • Raylene A. Reimer

    (University of Calgary
    University of Calgary
    University of Calgary)

  • Marie-Claire Arrieta

    (University of Calgary
    University of Calgary
    University of Calgary
    University of Calgary)

Abstract

The gut microbiome causally contributes to obesity; however, the role of fungi remains understudied. We previously identified three core species of the infant gut mycobiome (Rhodotorula mucilaginosa, Malassezia restricta and Candida albicans) that correlated with body mass index, however their causal contributions to obesity development are unknown. Here we show the effects of early-life colonization by these fungal species on metabolic health in gnotobiotic mice fed standard (SD) or high-fat-high-sucrose (HFHS) diets. Each species resulted in bacterial microbiome compositional and functional differences. R. mucilaginosa and M. restricta increased adiposity in mice fed SD, while only R. mucilaginosa exacerbated metabolic disease. In contrast, C. albicans resulted in leanness and resistance to diet-induced obesity. Intestinal nutrient transporter expression was unaffected by the presence of fungi in jejunal enteroids, yet the immune landscape in white adipose tissue was distinctly impacted by each fungal species, suggesting that these phenotypes may be a result of fungal immune regulation. This work revealed that three common fungal colonizers have distinct causal influences on obesity and metabolic inflammation and justifies the consideration of fungi in microbiome research on host metabolism.

Suggested Citation

  • Mackenzie W. Gutierrez & Erik van Tilburg Bernardes & Ellen Ren & Kristen N. Kalbfleisch & Madeline Day & Ewandson Luiz Lameu & Thaís Glatthardt & Emily M. Mercer & Sunita Sharma & Hong Zhang & Ali Al, 2025. "Early-life gut mycobiome core species modulate metabolic health in mice," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56743-8
    DOI: 10.1038/s41467-025-56743-8
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    References listed on IDEAS

    as
    1. Valentina Tremaroli & Fredrik Bäckhed, 2012. "Functional interactions between the gut microbiota and host metabolism," Nature, Nature, vol. 489(7415), pages 242-249, September.
    2. Erik van Tilburg Bernardes & Veronika Kuchařová Pettersen & Mackenzie W. Gutierrez & Isabelle Laforest-Lapointe & Nicholas G. Jendzjowsky & Jean-Baptiste Cavin & Fernando A. Vicentini & Catherine M. K, 2020. "Intestinal fungi are causally implicated in microbiome assembly and immune development in mice," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    3. Kirsty Brown & Carolyn A. Thomson & Soren Wacker & Marija Drikic & Ryan Groves & Vina Fan & Ian A. Lewis & Kathy D. McCoy, 2023. "Microbiota alters the metabolome in an age- and sex- dependent manner in mice," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Alessia Visconti & Caroline I. Le Roy & Fabio Rosa & Niccolò Rossi & Tiphaine C. Martin & Robert P. Mohney & Weizhong Li & Emanuele Rinaldis & Jordana T. Bell & J. Craig Venter & Karen E. Nelson & Tim, 2019. "Interplay between the human gut microbiome and host metabolism," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
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