ArticleHepatology (Baltimore, Md.)2025
Intestinal IL-33 promotes microbiota-derived trimethylamine N -oxide synthesis and drives metabolic dysfunction-associated steatotic liver disease progression by exerting dual regulation on HIF-1α.
Article in Hepatology (Baltimore, Md.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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.
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.
Who cites it
26 citing papers in PubMed.
- Omics-based Decoding of Metabolic Dysfunction-associated Fatty Liver Disease: From Pathogenesis to Clinical Translation.Journal of clinical and translational hepatology · 2026Review
- Metabolic dysfunction-associated steatotic liver disease: pathogenic mechanisms and exercise-induced molecular adaptations.Lipids in health and disease · 2026Review
- Systemic metabolic dysfunction drives platelet-mediated inflammation, fibrogenesis, and hepatocarcinogenesis in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Ginsenosides: potential therapeutic agents against hepatic fibrosis.Journal of ginseng research · 2026Review
- Review
- Bile Acids and the Gut-X Axis: TCM-Mediated Systemic Protection and Therapeutic Opportunities for Multi-Organ Diseases.Metabolites · 2026Review
- The Gut-Liver Axis in MASLD: From Host-Microbiome Crosstalk to Precision Therapeutics.Microorganisms · 2026Review
- The "Immune Rebellion" from the Intestines to the Liver: A Vicious Cycle That Causes the Liver to Collapse.Metabolites · 2026Review
- [Periodontitis and Metabolic Dysfunction-Associated Fatty Liver Disease: From Oral Dysbiosis to Hepatic Metabolic Dysregulation].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Review
- Functional roles and regulatory mechanisms of paeonol in the treatment of liver disease.Natural products and bioprospecting · 2026Review
- Gut microbiomes-host immune response and organ dysfunction across the gut-lung, gut-brain, and gut-liver axes.Frontiers in cellular and infection microbiology · 2026Review
- Gut microbiota and the gut-liver axis in MASLD: mechanisms, immune regulation and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- Targeting gut dysbiosis: a new frontier in MASLD management.Frontiers in systems biology · 2026Review
- Spatial immune dysregulation in MASLD: integration of lobular zoning, metabolism and immune function.Frontiers in immunology · 2026Review
- The macrophage opera: from metabolic prolog to oncogenic crescendo in metabolic dysfunction-associated steatotic liver disease.Frontiers in medicine · 2026Review
- Critical role of interleukin-33 in pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease.Frontiers in medicine · 2026Review
- Fucoidan Therapy for Extraintestinal Diseases: Targeting the Microbiota-Gut-Organ Axes.Biomolecules · 2025Review
- Docosahexaenoic acid (DHA) alleviates hepatic lipid deposition in dairy cows during the transition period: an integrated in vitro and in vivo study.Journal of animal science and biotechnology · 2025Article
- Article
- Sodium butyrate alleviates DSS-induced inflammatory bowel disease by inhibiting ferroptosis and modulating ERK/STAT3 signaling and intestinal flora.Annals of medicine · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsGut microbiota plays a prominent role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). IL-33 is highly expressed at mucosal barrier sites and regulates intestinal homeostasis. Herein, we aimed to investigate the role and mechanism of intestinal IL-33 in MASLD. APPROACH AND
resultsIn both humans and mice with MASLD, hepatic expression of IL-33 and its receptor suppression of tumorigenicity 2 (ST2) showed no significant change compared to controls, while serum soluble ST2 levels in humans, as well as intestinal IL-33 and ST2 expression in mice were significantly increased in MASLD. Deletion of global or intestinal IL-33 in mice alleviated metabolic disorders, inflammation, and fibrosis associated with MASLD by reducing intestinal barrier permeability and rectifying gut microbiota dysbiosis. Transplantation of gut microbiota from IL-33 deficiency mice prevented MASLD progression in wild-type mice. Moreover, IL-33 deficiency resulted in a decrease in the abundance of trimethylamine N -oxide-producing bacteria. Inhibition of trimethylamine N -oxide synthesis by 3,3-dimethyl-1-butanol mitigated hepatic oxidative stress in mice with MASLD. Nuclear IL-33 bound to hypoxia-inducible factor-1α and suppressed its activation, directly damaging the integrity of the intestinal barrier. Extracellular IL-33 destroyed the balance of intestinal Th1/Th17 and facilitated Th1 differentiation through the ST2- Hif1a - Tbx21 axis. Knockout of ST2 resulted in a diminished MASLD phenotype resembling that observed in IL-33 deficiency mice.
conclusionsIntestinal IL-33 enhanced gut microbiota-derived trimethylamine N -oxide synthesis and aggravated MASLD progression through dual regulation on hypoxia-inducible factor-1α. Targeting IL-33 and its associated microbiota may provide a potential therapeutic strategy for managing MASLD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.