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

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 and Marie-Claire Arrieta ()
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Mackenzie W. Gutierrez: University of Calgary
Erik van Tilburg Bernardes: University of Calgary
Ellen Ren: University of Calgary
Kristen N. Kalbfleisch: University of Calgary
Madeline Day: University of Calgary
Ewandson Luiz Lameu: University of Calgary
Thaís Glatthardt: University of Calgary
Emily M. Mercer: University of Calgary
Sunita Sharma: University of Calgary
Hong Zhang: University of Calgary
Ali Al-Azawy: University of Calgary
Faye Chleilat: University of Calgary
Simon A. Hirota: University of Calgary
Raylene A. Reimer: University of Calgary
Marie-Claire Arrieta: University of Calgary

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-56743-8

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