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Fluoride exposure-induced gut microbiota alteration mediates colonic ferroptosis through N6-methyladenosine (m6A) mediated silencing of SLC7A11

Huang, Haonan, Lin, Yu, Xin, Jinge, Sun, Ning, Zhao, Zhifang, Wang, Hesong, Duan, Lixiao, Zhou, Yanxi, Liu, Xingmei, Fang, Jing, Jing, Bo, Pan, Kangcheng, Zeng, Yan, Zeng, Dong, Li, Hao, Ma, Hailin, Bai, Yang, Wei, Limin, Ni, Xueqin·2024·Ecotoxicology and Environmental Safety
DOI 10.1016/j.ecoenv.2024.116816
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Abstract

Fluoride exposure is widespread worldwide and poses a significant threat to organisms, particularly to their gastrointestinal tracts. However, due to limited knowledge of the mechanism of fluoride induced intestinal injury, it has been challenging to develop an effective treatment. To address this issue, we used a series of molecular biology in vitro and in vivo experiments. NaF triggered m 6 A mediated ferroptosis to cause intestinal damage. Mechanistically, NaF exposure increased the m 6 A level of SLC7A11 mRNA, promoted YTHDF2 binding to m 6 A-modified SLC7A11 mRNA, drove the degradation of SLC7A11 mRNA, and led to a decrease in its protein expression, which eventually triggers ferroptosis. Moreover, NaF aggravated ferroptosis of the colon after antibiotics destroyed the composition of gut microbiota. 16 S rRNA sequencing and SPEC-OCCU plots, Zi-Pi relationships, and Spearman correlation coefficients verified that Lactobacillus murinus (ASV54, ASV58, and ASV82) plays a key role in the response to NaF-induced ferroptosis. Collectively, NaF-induced gut microbiota alteration mediates severe intestinal cell injury by inducing m 6 A modification-mediated ferroptosis. Our results highlight a key mechanism of the gut in response to NaF exposure and suggest a valuable theoretical basis for its prevention and treatment.

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Metadata

Authors
Huang, H., Lin, Y., Xin, J., Sun, N., Zhao, Z., Wang, H., Duan, L., Zhou, Y., Liu, X., Fang, J., Jing, B., Pan, K., Zeng, Y., Zeng, D., Li, H., Ma, H., Bai, Y., Wei, L., & Ni, X.
Venue
Ecotoxicology and Environmental Safety
Publisher
Elsevier BV
Published
2024-09
Volume
283
Pages
116816
ISSN
0147-6513
DOI
10.1016/j.ecoenv.2024.116816
Cited by
15
References
2
Language
en
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