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

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 th...

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Main Authors: 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-Azawy, Faye Chleilat, Simon A. Hirota, Raylene A. Reimer, Marie-Claire Arrieta
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56743-8
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author 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-Azawy
Faye Chleilat
Simon A. Hirota
Raylene A. Reimer
Marie-Claire Arrieta
author_facet 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-Azawy
Faye Chleilat
Simon A. Hirota
Raylene A. Reimer
Marie-Claire Arrieta
author_sort Mackenzie W. Gutierrez
collection DOAJ
description 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.
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spelling doaj-art-4e9491be2b1b49d386965e929b3523562025-02-09T12:46:31ZengNature PortfolioNature Communications2041-17232025-02-0116111710.1038/s41467-025-56743-8Early-life gut mycobiome core species modulate metabolic health in miceMackenzie W. Gutierrez0Erik van Tilburg Bernardes1Ellen Ren2Kristen N. Kalbfleisch3Madeline Day4Ewandson Luiz Lameu5Thaís Glatthardt6Emily M. Mercer7Sunita Sharma8Hong Zhang9Ali Al-Azawy10Faye Chleilat11Simon A. Hirota12Raylene A. Reimer13Marie-Claire Arrieta14Department of Pediatrics, University of CalgaryDepartment of Pediatrics, University of CalgaryDepartment of Pediatrics, University of CalgaryDepartment of Pediatrics, University of CalgaryDepartment of Pediatrics, University of CalgaryInternational Microbiome Centre, Snyder Institute, University of CalgaryDepartment of Pediatrics, University of CalgaryDepartment of Pediatrics, University of CalgaryDepartment of Pediatrics, University of CalgaryDepartment of Physiology and Pharmacology, University of CalgaryDepartment of Pediatrics, University of CalgaryDepartment of Physiology and Pharmacology, University of CalgaryDepartment of Physiology and Pharmacology, University of CalgaryInternational Microbiome Centre, Snyder Institute, University of CalgaryDepartment of Pediatrics, University of CalgaryAbstract 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.https://doi.org/10.1038/s41467-025-56743-8
spellingShingle 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-Azawy
Faye Chleilat
Simon A. Hirota
Raylene A. Reimer
Marie-Claire Arrieta
Early-life gut mycobiome core species modulate metabolic health in mice
Nature Communications
title Early-life gut mycobiome core species modulate metabolic health in mice
title_full Early-life gut mycobiome core species modulate metabolic health in mice
title_fullStr Early-life gut mycobiome core species modulate metabolic health in mice
title_full_unstemmed Early-life gut mycobiome core species modulate metabolic health in mice
title_short Early-life gut mycobiome core species modulate metabolic health in mice
title_sort early life gut mycobiome core species modulate metabolic health in mice
url https://doi.org/10.1038/s41467-025-56743-8
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