ArticleThe Journal of clinical investigation2019
Antibiotic pretreatment alleviates liver transplant damage in mice and humans.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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
60 citing papers in PubMed, 97 citations in OpenAlex.
- Review
- Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- The gut microbiome in solid-organ and haematopoietic-stem-cell transplantation.Nature reviews. Microbiology · 2026Review
- Mechanistic investigation of the crosstalk between hepatic ischemia-reperfusion injury and intestinal microbiota.Translational gastroenterology and hepatology · 2026Review
- Rab23 GTPase and IFT43 regulate the trafficking of prostaglandin E receptor 4 to primary cilia.Communications biology · 2025Article
- Article
- Hepatic ischemia-reperfusion injury: Underlying mechanisms and concepts in liver surgery and liver transplantation.Hepatology (Baltimore, Md.) · 2025Article
- Rebamipide Induces Hair Regeneration Through EP4-Driven Lipid Metabolism Remodeling.International journal of molecular sciences · 2025Article
- Mouse orthotopic liver transplantation: Challenges, achievements, and applications.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Review
- Obesity-associated Inflammation and Alloimmunity.Transplantation · 2025Review
- Bifidobacterium bifidum reduces oxidative stress and alters gut flora to mitigate acute liver injury caused by N-acetyl-p-aminophenol.BMC microbiology · 2025Article
- Gut Microbiota-Mediated Alterations of Hippocampal CB1R Regulating the Diurnal Variation of Cognitive Impairment Induced by Hepatic Ischemia-Reperfusion Injury in Mice.Neurochemical research · 2024Article
- White-light activatable organic NIR-II luminescence nanomaterials for imaging-guided surgery.Nature communications · 2024Article
- Advancements in understanding the role of intestinal dysbacteriosis mediated mucosal immunity in IgA nephropathy.BMC nephrology · 2024Review
- The Microbiome and Pediatric Transplantation.Journal of the Pediatric Infectious Diseases Society · 2024Review
- Cold stress-induced ferroptosis in liver sinusoidal endothelial cells determines liver transplant injury and outcomes.JCI insight · 2024Article
- Association between amoxicillin administration and outcomes in critically ill patients with acute kidney injury.Frontiers in pharmacology · 2024Article
- Gut microbiota regulates circadian oscillation in hepatic ischemia-reperfusion injury-induced cognitive impairment by interfering with hippocampal lipid metabolism in mice.Hepatology international · 2023Article
- Role of the immune system in liver transplantation and its implications for therapeutic interventions.MedComm · 2023Review
- Unfolded Protein Response Signaling in Liver Disorders: A 2023 Updated Review.International journal of molecular sciences · 2023Review
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Commented on by
- Commented on by
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Although modifications of gut microbiota with antibiotics (Abx) influence mouse skin and cardiac allografts, its role in orthotopic liver transplantation (OLT) remains unknown. We aimed to determine whether and how recipient Abx pretreatment may affect hepatic ischemia-reperfusion injury (IRI) and OLT outcomes. Mice (C57BL/6) with or without Abx treatment (10 days) were transplanted with allogeneic (BALB/c) cold-stored (18 hours) livers, followed by liver and blood sampling (6 hours). We divided 264 human OLT recipients on the basis of duration of pre-OLT Abx treatment into control (Abx-free/Abx <10 days; n = 108) and Abx treatment (Abx ≥10days; n = 156) groups; OLT biopsy (Bx) samples were collected 2 hours after OLT (n = 52). Abx in mice mitigated IRI-stressed OLT (IRI-OLT), decreased CCAAT/enhancer-binding protein homologous protein (CHOP) (endoplasmic reticulum [ER] stress), enhanced LC3B (autophagy), and inhibited inflammation, whereas it increased serum prostaglandin E2 (PGE2) and hepatic PGE2 receptor 4 (EP4) expression. PGE2 increased EP4, suppressed CHOP, and induced autophagosome formation in hepatocyte cultures in an EP4-dependent manner. An EP4 antagonist restored CHOP, suppressed LC3B, and recreated IRI-OLT. Remarkably, human recipients of Abx treatment plus OLT (Abx-OLT), despite severe pretransplantation clinical acuity, had higher EP4 and LC3B levels but lower CHOP levels, which coincided with improved hepatocellular function (serum aspartate aminotransferase/serum aspartate aminotransferase [sALT/sAST]) and a decreased incidence of early allograft dysfunction (EAD). Multivariate analysis identified "Abx-free/Abx <10 days" as a predictive factor of EAD. This study documents the benefits of Abx pretreatment in liver transplant recipients, identifies ER stress and autophagy regulation by the PGE2/EP4 axis as a homeostatic underpinning, and points to the microbiome as a therapeutic target in OLT.
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.