Evidence map›Paper›PMID 40410722›Full record

ArticleMolecular medicine (Cambridge, Mass.)2025

ITIH4 alleviates OVA-induced asthma by regulating lung-gut microbiota.

Yi-Hsuan Liu, Yueh-Lun Lee, Chia-Li Han, Yu-Chun Lo, Zih-An Liao, Yu-Syuan Shih, Yi-Wen Lin, Syue-Wei Peng, Kang-Yun Lee, Shu-Chuan Ho and 5 more

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Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Yi-Hsuan Liu *School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
Yueh-Lun Lee *Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Chia-Li HanMaster Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Yu-Chun LoThe Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Zih-An LiaoSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
Yu-Syuan ShihSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
Yi-Wen LinSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
Syue-Wei PengSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
Kang-Yun LeeDivision of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Shu-Chuan HoSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
Sheng-Ming WuDivision of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Cheng-Wei LinGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Kian Fan ChungNational Heart and Lung Institute, Imperial College London, London, UK.
Jer-Hwa ChangSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan. m102094030@tmu.edu.tw.
Hsiao-Chi ChuangSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan. chuanghc@tmu.edu.tw.

Funding

National Science and Technology Council 112-2628-B-038-010-MY3
6 · The paper itself

Abstract

backgroundInter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), a Type 2 acute phase protein, is critical for resolving inflammation and promoting tissue repair. While its role in chronic respiratory diseases is recognized, its effects on asthma remain unclear. This study investigated the effects of ITIH4 on the modulation of lung and gut microbiota, the attenuation of allergic inflammation, and the improvement of respiratory outcomes in an asthma mouse model.

methodsSix-week-old male Balb/c mice were divided into five groups: control, ITIH4, ovalbumin (OVA), and two OVA + ITIH4 treatment groups at different doses. Lung function and oxygen saturation were measured, and bronchoalveolar lavage fluid (BALF) was analyzed for white blood cell counts and cytokines. Lung and gut microbiota were profiled using 16 S rRNA gene sequencing, and short-chain fatty acids (SCFAs) were measured using gas chromatography-mass spectrometry (GC-MS). Proteomic profiling of intestinal tissues was conducted to identify ITIH4-associated signaling pathways.

resultsITIH4 administration significantly mitigated OVA-induced asthma symptoms by reducing weight loss, airway resistance, and tissue damping (p < 0.05). Histological analysis showed decreased airway wall thickening and lung injury scores (p < 0.05). ITIH4 also lowered BALF eosinophils and lymphocytes, IgE, and Th2 cytokines (IL-4, IL-5, and IL-13) (p < 0.05). ITIH4 treatment modulated microbiome composition, enriching Gram-positive taxa (Nocardioidaceae and Acholeplasmataceae) and depleting Gram-negative Helicobacteraceae (p < 0.05). SCFAs correlated with microbiome alterations, notably reduced 4-methylpentanoic acid levels (p < 0.05). Proteomic analysis revealed a dose-dependent activation of granzyme A signaling and suppression of metabolic and solute transport pathways.

conclusionsITIH4 ameliorates asthma symptoms by modulating lung and gut microbiota, dampening Th2-driven inflammation, and restoring mucosal immune balance. These findings support ITIH4 as a potential candidate for microbiome-targeted asthma therapy.

Indexed as

AsthmaGastrointestinal MicrobiomeLungAnimalsBronchoalveolar Lavage FluidCytokinesDisease Models, AnimalMaleMiceMice, Inbred BALB COvalbuminCytokinesOvalbuminAirway hyperresponsivenessInflammationMicrobiomeShort-chain fatty acidTh2

Identifiers

PMID40410722
PMCPMC12102971

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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.