Evidence map›Paper›PMID 40673634›Full record

ArticleClinical and translational medicine2025

Itaconate suppresses neonatal intestinal inflammation via metabolic reprogramming of M1 macrophage.

Shuchen Huangfu, Chaoting Lan, Sitao Li, Huijuan Wang, Chun Yan, Yuling Yang, Bowen Tian, Yide Mu, Peizhi Zhao, Yan Tian and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

6 citing papers in PubMed.

  1. Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026
    Review
  2. Review
  3. Role of itaconate in intestinal disease (Review).International journal of molecular medicine · 2026
    Review
  4. Dysregulated immunometabolism in gut inflammation.Acta biochimica et biophysica Sinica · 2026
    Review
  5. Review
  6. Article
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

15 authors.

Shuchen HuangfuCenter for Medical Research on Innovation and Translation, Guangzhou First People' s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong, China.
Chaoting LanDepartment of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, China.
Sitao LiDepartment of Pediatrics, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Huijuan WangCenter for Medical Research on Innovation and Translation, Guangzhou First People' s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong, China.
Chun YanCenter for Medical Research on Innovation and Translation, Guangzhou First People' s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong, China.
Yuling YangCenter for Medical Research on Innovation and Translation, Guangzhou First People' s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong, China.
Bowen TianDepartment of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, China.
Yide MuDepartment of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, China.
Peizhi ZhaoDepartment of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, China.
Yan TianDepartment of Anesthesiology, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi, China.
Yijia WangDepartment of Pediatrics, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Wei ZhongDepartment of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, China.
Limei ZhongDepartment of Laboratory Medicine, the Affliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, China.
Yongyan ShiDivision of Neonatology, Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Yufeng LiuCenter for Medical Research on Innovation and Translation, Guangzhou First People' s Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong, China.ORCID 0009-0002-4794-3316

Funding

345 Talent Project of Shengjing Hospital M1392Jiangxi Provincial Children's Hospital 2024 First Batch "Qingmiao" Scientific Research Projects 2024JXEYQM02National Natural Science Funds 82171695National Natural Science Funds 82171709National Natural Science Funds 82301955National Natural Science Funds 82370526Research Foundation of Guangzhou Women and Children's Medical Center for Clinical Doctor 2023BS015Science and Technology Program of Guangzhou SL2024A03J01319Science and Technology Program of Guangzhou SL2024A04J00240Science and Technology Project of Guangzhou 2024A03J1171Science and Technology Project of Guangzhou 2024A03J1238the China Postdoctor Science Foundation 2023M730791the Guangdong Basic and Applied Basic Research Foundation 2024A1515013190the Science and Technology Research Project of Education Department of Jiangxi Province GJJ2203559
6 · The paper itself

Abstract

backgroundNecrotizing enterocolitis (NEC) is a rapidly progressive and severe gastrointestinal disorder in neonates that is marked by an inflammatory cascade initiated by mechanisms that remain incompletely understood, resulting in intestinal necrosis and systemic infections. This study demonstrated that itaconate (ITA) exerts a protective effect in NEC by regulating macrophage reprogramming.

methodsChanges in ITA expression were investigated using immunofluorescence staining and liquid chromatography-mass spectrometry, and their effect on immune cell differentiation was verified through single-cell sequencing. In vivo experiments were performed using ACOD1

resultsWe detected changes in ITA expression in clinical NEC samples and confirmed the effect of these changes on immune cell differentiation. In vivo experiments confirmed the therapeutic role of ITA in regulating macrophage differentiation in NEC, and we further investigated the mechanism by which ITA regulates macrophage metabolic reprogramming. The depletion of ITA in NEC correlates with an increased frequency of pro-inflammatory macrophage polarization, thereby exacerbating intestinal inflammatory injury. Importantly, our in vivo experiments revealed that treatment with 4-octyl itaconate (4OI) significantly mitigated intestinal symptoms associated with NEC in murine models. Mechanistic investigations showed that 4OI effectively suppressed M1 macrophage polarization by rescuing mitochondrial function and upregulating oxidative phosphorylation in macrophages.

conclusionsOur results highlight ITA as a metabolic checkpoint of macrophage differentiation in NEC and suggest the therapeutic efficacy of 4OI in NEC. KEY POINTS: Itaconate alleviates NEC by reprogramming M1 macrophage metabolism ACOD1 deficiency exacerbates NEC severity 4OI maintains intestinal barrier integrity. 4OI rescues NEC by regulating macrophage mitochondrial activity.

Indexed as

Enterocolitis, NecrotizingInflammationMacrophagesSuccinatesAnimalsAnimals, NewbornDisease Models, AnimalHumansInfant, NewbornIntestinesMetabolic ReprogrammingMiceitaconic acidSuccinatesitaconatemacrophagemetabolic reprogrammingnecrotizing enterocolitisoxidative phosphorylation

Identifiers

PMID40673634
PMCPMC12268792

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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 OpenQuestion graph.