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5-Fluorouracil causes intestinal damage via gut microbiota-mediated ferroptosis and innate immunity in Drosophila melanogaster and mice
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Xiaoqian WANG1, Minghui XIU1,2, Linghui CHANG1, Jinhan WU2, Yan WANG2, Jianzheng HE1,3,4, Yongqi LIU2,3. 5-Fluorouracil causes intestinal damage via gut microbiota-mediated ferroptosis and innate immunity in Drosophila melanogaster and mice[J]. Journal of Zhejiang University Science B, 1998, -1(-1): .
@article{title="5-Fluorouracil causes intestinal damage via gut microbiota-mediated ferroptosis and innate immunity in Drosophila melanogaster and mice",
author="Xiaoqian WANG1, Minghui XIU1,2, Linghui CHANG1, Jinhan WU2, Yan WANG2, Jianzheng HE1,3,4, Yongqi LIU2,3",
journal="Journal of Zhejiang University Science B",
volume="-1",
number="-1",
pages="",
year="1998",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2500346"
}
%0 Journal Article
%T 5-Fluorouracil causes intestinal damage via gut microbiota-mediated ferroptosis and innate immunity in Drosophila melanogaster and mice
%A Xiaoqian WANG1
%A Minghui XIU1
%A 2
%A Linghui CHANG1
%A Jinhan WU2
%A Yan WANG2
%A Jianzheng HE1
%A 3
%A 4
%A Yongqi LIU2
%A 3
%J Journal of Zhejiang University SCIENCE B
%V -1
%N -1
%P
%@ 1673-1581
%D 1998
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2500346
TY - JOUR
T1 - 5-Fluorouracil causes intestinal damage via gut microbiota-mediated ferroptosis and innate immunity in Drosophila melanogaster and mice
A1 - Xiaoqian WANG1
A1 - Minghui XIU1
A1 - 2
A1 - Linghui CHANG1
A1 - Jinhan WU2
A1 - Yan WANG2
A1 - Jianzheng HE1
A1 - 3
A1 - 4
A1 - Yongqi LIU2
A1 - 3
J0 - Journal of Zhejiang University Science B
VL - -1
IS - -1
SP -
EP -
%@ 1673-1581
Y1 - 1998
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2500346
Abstract: Chemotherapy-induced intestinal mucositis (IM) severely impacts cancer prognosis, yet effective therapies remain limited due to unclear mechanisms. This study aimed to establish a 5-Fluorouracil (5-FU)-induced IM model in drosophila melanogaster (flies). The results revealed that 5-FU caused systemic and intestinal damage in flies, including reduced survival rate, starvation resistance, development, excretion, crop motility and intestinal length; disrupted acid-base homeostasis; and increased enterocyte death. The combined analysis of transcriptomics, bioinformatics, and microbiomics demonstrated that intestinal damage induced by 5-FU was associated with gut microbiota imbalance, ferroptosis, and innate immunity. 5-FU consistently activated ferroptosis in flies, including increased reactive oxygen species (ROS), malondialdehyde (MDA), total Fe2?, lipid peroxidation, and the expression of key ferroptosis-related genes. ferroptosis inhibitor improved survival rates and intestinal damage in 5-FU-treated flies. Furthermore, antibiotic depletion of gut microbiota alleviated intestinal damage and down-regulated innate immune and ferroptosis markers in 5-FU-induced flies. Conversely, fecal microbiota transplantation (FMT) from 5-FU-induced flies was sufficient to recapitulate intestinal injury in healthy flies. 5-FU also consistently induced intestinal damage and ferroptosis in mice, including increased ROS, ACSL4, and 4-HNE levels, and decreased GPX4. This study implicates gut microbiota-driven ferroptosis and innate immunity in 5-FU-induced IM, establishing drosophila melanogaster as a powerful model for mechanistic discovery and drug screening.
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