A gut symbiotic filamentous fungus reprograms host metabolism and the microbiota to confer radioprotection

The gut mycobiome is increasingly linked to host physiology, yet functional insights are dominated by yeasts, leaving the roles of filamentous fungi largely unexplored. Here, we identify Mucor racemosus as a gut-resident symbiotic filamentous fungus that establishes intestinal colonization via both hyphal and spore forms. M. racemosus confers radioprotection through an integrated metabolic program coupling direct host support with microbiota-mediated amplification. The fungus produces L-glutamate, L-aspartate, and DL-lysine, which are transferred to the host to enhance DNA damage repair in radiation-exposed intestinal epithelial cells. In parallel, M. racemosus –derived methylthioadenosine remodels the gut bacterial community by enriching Limosilactobacillus reuteri and reprogramming sulfur metabolism to generate radioprotective methionine. This coordinated fungal–bacterial metabolic axis reinforces intestinal radiotolerance. Consistent with this mechanism, dietary administration of M. racemosus –fermented cheese confers radioprotection in vivo. Together, these findings establish gut filamentous fungi as active metabolic organizers of host–microbiota interactions.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2026-08-25
DOI
https://doi.org/10.1073/pnas.2608386123
Primary Topic
Effects of Radiation Exposure
Type
article
Field-Weighted Citation Impact
0.00

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article

A gut symbiotic filamentous fungus reprograms host metabolism and the microbiota to confer radioprotection

Xingzhong Liu, Ming Cui, Xiaozhou Zeng, Xiaojing Liu et al.
Proceedings of the National Academy of Sciences
Effects of Radiation Exposure
article

A gut symbiotic filamentous fungus reprograms host metabolism and the microbiota to confer radioprotection

Xingzhong Liu, Ming Cui, Xiaozhou Zeng, Xiaojing Liu, Jia Liu, Jiamin Zhao, Huiwen Xiao, Bin Wang, Zhihong Liu, Yuan Li, Jiali Dong
article en

Abstract

The gut mycobiome is increasingly linked to host physiology, yet functional insights are dominated by yeasts, leaving the roles of filamentous fungi largely unexplored. Here, we identify Mucor racemosus as a gut-resident symbiotic filamentous fungus that establishes intestinal colonization via both hyphal and spore forms. M. racemosus confers radioprotection through an integrated metabolic program coupling direct host support with microbiota-mediated amplification. The fungus produces L-glutamate, L-aspartate, and DL-lysine, which are transferred to the host to enhance DNA damage repair in radiation-exposed intestinal epithelial cells. In parallel, M. racemosus –derived methylthioadenosine remodels the gut bacterial community by enriching Limosilactobacillus reuteri and reprogramming sulfur metabolism to generate radioprotective methionine. This coordinated fungal–bacterial metabolic axis reinforces intestinal radiotolerance. Consistent with this mechanism, dietary administration of M. racemosus –fermented cheese confers radioprotection in vivo. Together, these findings establish gut filamentous fungi as active metabolic organizers of host–microbiota interactions.

Proceedings of the National Academy of SciencesVol. 123(35)
Tianjin University of Technology (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Nankai University (CN), Soochow University (CN), Second Affiliated Hospital of Soochow University (CN), Kementerian Pendidikan Malaysia (MY)
National Natural Science Foundation of China
Openalex Percentile: Top 10%
Effects of Radiation Exposure
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