Evidence map›Paper›PMID 42571027›Full record

ArticleJournal of animal science and biotechnology2026

Fisetin alleviates zinc overload-induced intestinal injury by inhibiting ferroptosis and remodeling gut microbiota in weaned piglets.

Feifei Huang, Yuhang Deng, Mohan Zhou, Huangen Xu, Jie Feng

Abstract read
In one paragraph

Article in Journal of animal science and biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Feifei HuangKey Laboratory of Nutrition and Breeding for High-Quality Animal Products of Zhejiang Province, College of Animal Science, Zhejiang University, Hangzhou, 310058, China.
Yuhang DengKey Laboratory of Animal Molecular Nutrition Ministry of Education, College of Animal Science, Zhejiang University, Hangzhou, 310058, China.
Mohan ZhouKey Laboratory of Animal Molecular Nutrition Ministry of Education, College of Animal Science, Zhejiang University, Hangzhou, 310058, China.
Huangen XuResearch Center of Zhejiang Kesheng Feed Co., Ltd., Shaoxing, 312000, Zhejiang, China. xhg@sx.net.cn.
Jie FengKey Laboratory of Nutrition and Breeding for High-Quality Animal Products of Zhejiang Province, College of Animal Science, Zhejiang University, Hangzhou, 310058, China. fengj@zju.edu.cn.ORCID https://orcid.org/0000-0002-2690-429X

Funding

Key Research and Development Program of Zhejiang Province 2026C02A1021National Key Research and Development Program of China 2022YFD1300504
6 · The paper itself

Abstract

backgroundHigh doses of zinc oxide (ZnO) effectively prevent post-weaning diarrhea and promote growth in weaned piglets, but raise concerns over intestinal injury, metabolic disorders, and risks of fostering bacterial resistance. This study aimed to identify non-chelating polyphenols capable of mitigating zinc toxicity and to elucidate their protective mechanisms, with emphasis on ferroptosis inhibition.

resultsNetwork toxicology predicted ferroptosis as a central mechanism in zinc-induced intestinal injury, which was confirmed in intestinal epithelial cells where zinc overload specifically induced ferroptosis without activating apoptosis, necroptosis, or autophagy. From multiple polyphenols, fisetin (FIS) was identified as a non-chelating candidate that alleviated zinc-induced cytotoxicity, preserved tight junction proteins, and activated the Nrf2-GPX4 axis to inhibit ferroptosis in vitro. In zinc-overloaded weaned piglets, FIS supplementation maintained the growth-promoting effects of high-dose zinc while ameliorating intestinal damage. FIS also attenuated oxidative stress, alleviated inflammation, and inhibited ferroptosis in the jejunum. Furthermore, FIS remodeled the gut microbiota, enriching beneficial taxa Romboutsia (positively correlated with growth performance) and Clostridium_sensu_stricto_1 (positively correlated with the p-Nrf2/Nrf2 ratio), while suppressing the zinc-enriched Anaerovibrio (negatively correlated with GPX4 protein expression). FIS also shifted microbial metabolic pathways toward amino acid and terpenoid metabolism, potentially contributing to the observed ferroptosis defense.

conclusionFIS alleviates high-dose ZnO-induced intestinal injury in weaned piglets through dual modulation, activating the Nrf2-GPX4 axis to inhibit ferroptosis and remodeling the gut microbiota to reinforce this defense. By preserving the growth benefits of zinc while mitigating its toxicity, FIS represents a promising nutritional strategy for sustainable swine production.

Indexed as

FerroptosisFisetinIntestinal healthWeaned pigletsZinc overload

Identifiers

PMID42571027
PMCPMC13453087

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.