ArticleJournal of hepatology2018
Gut microbiota mediates diurnal variation of acetaminophen induced acute liver injury in mice.
Article in Journal of hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05465642 (Alterations of Gut Microbiota and Serum Biochemical Markers in Asian Patients With Drug-induced Liver Injury), which is not on this map. Cited by 135 papers.
What it found
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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.
Alterations of Gut Microbiota and Serum Biochemical Markers in Asian Patients With Drug-induced Liver Injury
Who cites it
135 citing papers in PubMed, 251 citations in OpenAlex.
- Gut Microbiota Participates in Antithyroid Drug Induced Liver Injury Through the Lipopolysaccharide Related Signaling Pathway.Frontiers in pharmacology · 2020Trial
- Boosting oral bioavailability of taraxasterol via a nanocrystal-mucoadhesive micropatch platform for potent multi-mechanistic protection against drug-induced liver injury.Materials today. Bio · 2026Article
- Extract from Eucommia ulmoides Oliv. Leaves alleviates APAP-induced acute liver injury via reshaping gut microbiota and attenuating microbial bile acids metabolism disorder.Chinese medicine · 2026Article
- Circadian regulation of hepatic detoxification: implications for drug-induced liver injury.Archives of toxicology · 2026Review
- The gut-liver axis in drug-induced liver injury (DILI): Interplay between gut microbiota, intestinal barrier, and immune system.Acta pharmaceutica Sinica. B · 2026Review
- Circadian rhythms and microbiota: molecular crosstalk and its implications for health and disease.Biology direct · 2026Review
- Modulation of gut microbiota and its metabolite Equol by Huaier granule suppresses hepatocellular carcinoma via the gut-liver axis.NPJ biofilms and microbiomes · 2026Article
- Article
- Uremic Clearance Granules Regulate Immune Equilibrium via Gut Microbiome to Alleviate Chronic Renal Failure.Biomaterials research · 2026Article
- Alterations in gut microbiota and metabolites contribute to postoperative sleep disturbances.Animal models and experimental medicine · 2025Article
- Diurnal oscillations of amino acids dynamically associate with microbiota and resistome in the colon of pigs.Animal microbiome · 2025Article
- Gram-positive probiotics improves acetaminophen-induced hepatotoxicity by inhibiting leucine and Hippo-YAP pathway.Cell & bioscience · 2025Article
- Article
- Involvement of gut microbiota in chlorpyrifos-induced subchronic toxicity in mice.Archives of toxicology · 2025Article
- Maternal Gut Inflammation Aggravates Acute Liver Failure Through Facilitating Ferroptosis via Altering Gut Microbial Metabolism in Offspring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Bifidobacterium bifidum reduces oxidative stress and alters gut flora to mitigate acute liver injury caused by N-acetyl-p-aminophenol.BMC microbiology · 2025Article
- Oral administration of astilbin mitigates acetaminophen-induced acute liver injury in mice by modulating the gut microbiota.Acta pharmacologica Sinica · 2025Article
- Microbial dysbiosis-associated NMDAR hyperfunction in post-infectious irritable bowel syndrome with visceral hypersensitivity.Gastroenterology report · 2025Article
- Hesperidin alleviated D-GalN/LPS induced acute liver injury in mice: insights into gut microbiota and the Nrf2/Keap1 pathway.Frontiers in microbiology · 2025Article
- Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsAcetaminophen (APAP) induced hepatotoxicity is a leading cause of acute liver failure worldwide. It is well established that the liver damage induced by acetaminophen exhibits diurnal variation. However, the detailed mechanism for the hepatotoxic variation is not clear. Herein, we aimed to determine the relative contributions of gut microbiota in modulating the diurnal variation of hepatotoxicity induced by APAP.
methodsMale Balb/C mice were treated with or without antibiotics and a single dose of orally administered APAP (300 mg/kg) at ZT0 (when the light is on-start of resting period) and ZT12 (when the light is off-start of active period).
resultsIn agreement with previous findings, hepatic injury was markedly enhanced at ZT12 compared with ZT0. Interestingly, upon antibiotic treatment, ZT12 displayed a protective effect against APAP hepatotoxicity similar to ZT0. Moreover, mice that received the cecal content from ZT12 showed more severe liver damage than mice that received the cecal content from ZT0. 16S sequencing data revealed significant differences in the cecal content between ZT0 and ZT12 in the compositional level. Furthermore, metabolomic analysis showed that the gut microbial metabolites were also different between ZT0 and ZT12. Specifically, the level of 1-phenyl-1,2-propanedione (PPD) was significantly higher at ZT12 than ZT0. Treatment with PPD alone did not cause obvious liver damage. However, PPD synergistically enhanced APAP-induced hepatic injury in vivo and in vitro. Finally, we found Saccharomyces cerevisiae, which could reduce intestinal PPD levels, was able to markedly alleviate APAP-induced liver damage at ZT12.
conclusionsThe gut microbial metabolite PPD was responsible, at least in part, for the diurnal variation of hepatotoxicity induced by APAP by decreasing glutathione levels. LAY SUMMARY: Acetaminophen (APAP) induced acute liver failure because of over dose is a leading public health problem. APAP-induced liver injury exhibits diurnal variation, specifically APAP causes more severe liver damage when taken at night compared with in the morning. Herein, we showed that gut microbial metabolite, 1-phenyl-1,2-propanedione is involved in the rhythmic hepatotoxicity induced by APAP, by depleting hepatic glutathione (an important antioxidant) levels. Our data suggest gut microbiota may be a potential target for reducing APAP-induced acute liver injury.
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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.