ArticleeLife2024
Gut microbiota-derived gamma-aminobutyric acid from metformin treatment reduces hepatic ischemia/reperfusion injury through inhibiting ferroptosis.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 14 citations in OpenAlex.
- Pathophysiological mechanisms of cell death affecting graft survival in liver transplantation.World journal of transplantation · 2026Review
- GABA as an Overlooked Mediator of Metformin Action: GABA-mediated Neuropsychiatric and Hepatoprotective Activities of Metformin.Annals of neurosciences · 2026Review
- Peripheral GABA Signaling in Metabolic Adaptation and Maladaptation.International journal of molecular sciences · 2026Review
- Deciphering the Anti-Tumor Mechanisms of Metformin Through Reprogramming of the Tumor Microenvironment.Cells · 2026Review
- Preconditioning with sufentanil confers protective effects in transplantation by attenuating hepatic ischemia-reperfusion injury.World journal of transplantation · 2026Review
- The interplay mechanisms between gut microbiota and ferroptosis in inflammatory bowel disease.Frontiers in immunology · 2026Review
- The gut microbiota-bile acid axis in liver transplantation: implications for postoperative complications and therapeutic strategies.Frontiers in microbiology · 2026Review
- Mechanistic investigation of the crosstalk between hepatic ischemia-reperfusion injury and intestinal microbiota.Translational gastroenterology and hepatology · 2026Review
- Intestinal amino acid metabolic response and its roles in inflammatory bowel disease.Cell communication and signaling : CCS · 2025Review
- Targeting sirtuin 1/nuclear factor erythroid 2-related factor 2/tumor necrosis factor-α pathway to modulate hepatic ischemia reperfusion-induced injury.World journal of hepatology · 2025Article
- Article
- Crosstalk between ferroptosis and miRNA in type 2 diabetes mellitus and possible therapeutic targeting.European journal of medical research · 2025Review
- Crosstalk Between Microbiome and Ferroptosis in Diseases: From Mechanism to Therapy.Comprehensive Physiology · 2025Review
- Nuclear receptor FXR inhibits ferroptosis to alleviate hepatic ischemia-reperfusion injury by targeting GPX4 in a mouse model.Journal of molecular histology · 2025Article
- Ferroptosis and gut microbiota: A new horizon in alcohol-associated liver disease management.Cellular and molecular life sciences : CMLS · 2025Review
- Lactobacillus reuteri-derived γ-amino butyric acid alleviates MPTP-induced Parkinson's disease through inhibiting ferroptosis via the AKT-GSK3β-GPX4 axis.NPJ Parkinson's disease · 2025Article
- From mechanisms to medicine: Ferroptosis as a Therapeutic target in liver disorders.Cell communication and signaling : CCS · 2025Review
- Phosphatidylserine-mediated uptake of extracellular vesicles by hepatocytes ameliorates liver ischemia-reperfusion injury.Apoptosis : an international journal on programmed cell death · 2025Article
- Review
- Gut microbiota-derived gamma-aminobutyric acid improves host appetite by inhibiting satiety hormone secretion.mSystems · 2024Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis through reshaped gut microbiota in mice, which was confirmed by the results of fecal microbiota transplantation treatment but showed the elimination of the beneficial effects when gut bacteria were depleted using antibiotics. Detailedly, through 16S rRNA and metagenomic sequencing, we identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria. This increase was further confirmed by the elevation of GABA synthesis key enzymes, glutamic acid decarboxylase and putrescine aminotransferase, in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated in GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, with GABA identified as a key metabolite.
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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.