ArticleCell & bioscience2023
Gut microbiota-derived tryptophan metabolites alleviate liver injury via AhR/Nrf2 activation in pyrrolizidine alkaloids-induced sinusoidal obstruction syndrome.
Article in Cell & bioscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 27 citations in OpenAlex.
- Gut-Intervertebral Disc Axis: Gut Microbiome-Driven Immune-Metabolic Imbalance and Intervertebral Disc Degeneration.Journal of cellular physiology · 2026Review
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- Gut Microbiota and Ageing: A Critical Crosstalk in Alcohol-Related Liver Disease.Microorganisms · 2026Review
- Fucoidan Attenuates Lead-Induced Liver Injury Associated with IGFBP1 and Gut Microbiota-Derived Tryptophol Metabolism.Marine drugs · 2026Article
- Cocoa-Based Plant Matrices in Glucose Metabolism: Bioactive Compounds and Redox Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- Targeting Gut Microbiota by DPP-4 Inhibitors in Obesity: Mechanistic Insights and Therapeutic Implications.Current nutrition reports · 2026Review
- Pyrrolizidine Alkaloid-Induced Hepatotoxicity: A Narrative Review on Molecular Mechanisms and Detoxification Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Towards microbiome-informed strategies for predicting and preventing pregnancy complications.Reproduction & fertility · 2026Review
- Article
- Gut microbial metabolites of amino acids in liver diseases.Gut microbes · 2025Review
- Dietary Guanidinoacetic Acid Supplementation Improves Growth Performance of Plateau Yaks Through Plasma Metabolome Modulation.Biology · 2025Article
- A large-scale human toxicogenomics resource for drug-induced liver injury prediction.Nature communications · 2025Article
- Multifaceted Role of Microbiota-Derived Indole-3-Acetic Acid in Human Diseases and Its Potential Clinical Application.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Maternal Gut Inflammation Aggravates Acute Liver Failure Through Facilitating Ferroptosis via Altering Gut Microbial Metabolism in Offspring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- [Rifaximin curative effect and mechanism on monocrotaline-induced hepatic sinusoidal obstruction syndrome in mice].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Article
- Langqing Meiduo Jiujie pills treatment attenuates acute liver injury in animals by regulating anti-oxidative stress and liver metabolism.Frontiers in pharmacology · 2025Article
- New insights into coordinated regulation of AHR promoter transcription; molecular mechanisms and therapeutic targets.International journal of biological sciences · 2025Review
- Hesperidin alleviated D-GalN/LPS induced acute liver injury in mice: insights into gut microbiota and the Nrf2/Keap1 pathway.Frontiers in microbiology · 2025Article
- Huaier relieves oxaliplatin-induced hepatotoxicity through activation of the PI3K/AKT/Nrf2 signaling pathway in C57BL/6 mice.Heliyon · 2024Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsHepatic sinusoidal obstruction syndrome (HSOS) is caused by toxic injury, such as pyrrolizidine alkaloids, to the liver sinusoidal endothelial cells, and the gut microbiota may be involved. However, the specific role and underlying mechanism of gut microbiota in HSOS is unknown.
methodsHSOS model was established by gavage of monocrotaline (MCT) in rats. Fecal microbiota transplantation (FMT) with HSOS-derived or healthy gut flora was also conducted to validate the role of gut microflora in MCT-induced liver injury. The microbial 16 s rRNA analysis and untargeted metabolomics analysis in the faeces were performed to identify HSOS-related flora and metabolites. Finally, by supplementation with specific tryptophan metabolites, such as indole-3-acetaldehyde (IAAld) and indole acetic acid (IAA), we further confirmed the role of tryptophan metabolism in HSOS and the role of the AhR/Nrf2 pathway in MCT-induced liver injury.
resultsMCT induced HSOS-like liver injury in rats with significantly altered gut microbiota. Particularly, some tryptophan-metabolizing bacteria reduced in MCT-treated rats, such as Bacteroides, Bifidobacterium, Lactobacillus and Clostridium, and accompanied by a decrease in microbial tryptophan metabolic activity and a series of tryptophan derivatives. Restoring the gut microbiota via FMT improved MCT-induced liver damage, while HSOS-derived gut microbiota aggravated the liver injury induced by MCT. Supplementation with microbial tryptophan derivatives (IAAld or IAA), or 6-formylindolo(3,2-b)carbazole (Ficz, an AhR agonist) could activate the AhR/Nrf2 signaling pathway, thereby attenuating the MCT-induced liver oxidative stress and liver sinusoidal endothelial cells injury.
conclusionsGut microbiota plays a critical role in MCT-induced HSOS, with inadequate microbial tryptophan metabolism in the gut and consequently a lower activity of the AhR/Nrf2 signaling pathway in the liver, which should be a potential target for the management of HSOS.
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