ArticleGut microbes
Phenylpropionic acid produced by gut microbiota alleviates acetaminophen-induced hepatotoxicity.
Article in Gut microbes. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- Effect of Lacticaseibacillus rhamnosus IDCC 3201 on irritable bowel syndrome with constipation: a randomized, double-blind, and placebo-controlled trial.Scientific reports · 2024Trial
- A commensal protozoan exacerbates acetaminophen-induced liver injury by producing free sphingosine.Gut microbes · 2026Article
- Citrus depressa peel extract and its polymethoxyflavones mitigate acetaminophen-induced chronic liver injury in mice through antioxidant activation, epigenetic regulation, and gut microbiota modulation.Journal of the science of food and agriculture · 2026Article
- Escherichia coli expressing the kpsM gene exacerbates drug-induced liver injury through up-regulating α1,2-fucosyltransferase and disturbing the host taurine metabolism-from animal models and clinical studies.Journal of advanced research · 2026Article
- Impact of acetaminophen on the growth kinetics and metabolite production of probiotic lactic acid bacteria.Biotechnology letters · 2026Article
- Metabolomics of Eryngium heterophyllum by UHPLC-QToF-MS and In Silico Insights Into Potential Metabolic Syndrome Targets.Chemistry & biodiversity · 2026Article
- The Bacterial Metabolite Lndole-3-Propionic Acid Alleviates Acetaminophen-Induced Acute Liver Injury Partly through the Aryl Hydrocarbon Receptor Pathway.Journal of microbiology and biotechnology · 2026Article
- The gut-liver axis in drug-induced liver injury (DILI): Interplay between gut microbiota, intestinal barrier, and immune system.Acta pharmaceutica Sinica. B · 2026Review
- Article
- Genomics-informed approach identifies which cell types regulate the metabolome.Bioinformatics (Oxford, England) · 2026Article
- Improvement of Insulin Resistance byMicroorganisms · 2026Article
- [Gut microbiota-associated metabolites with drug-induced liver injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Deficiency of osteopontin in gut epithelial cells enhances intestinal integrity by promoting gut renewal through the JAK3/STAT4 pathway in acetaminophen (APAP)-induced acute liver injury.Cell communication and signaling : CCS · 2026Article
- Functional potential of gut microbiota inFrontiers in microbiology · 2026Article
- Gut microbial metabolites of amino acids in liver diseases.Gut microbes · 2025Review
- The diet-derived gut microbial metabolite 3-phenylpropionic acid reverses insulin resistance and obesity-associated metabolic dysfunction.Molecular metabolism · 2025Article
- Gram-positive probiotics improves acetaminophen-induced hepatotoxicity by inhibiting leucine and Hippo-YAP pathway.Cell & bioscience · 2025Article
- Gut-X axis.iMeta · 2025Review
- Protective effects of Atractylodes macrocephala polysaccharides on acetaminophen-induced liver injury.Frontiers in pharmacology · 2025Article
- The Discovery of Gut Microbial Metabolites as Modulators of Host Susceptibility to Acetaminophen-Induced Hepatotoxicity.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The gut microbiota affects hepatic drug metabolism. However, gut microbial factors modulating hepatic drug metabolism are largely unknown. In this study, using a mouse model of acetaminophen (APAP)-induced hepatotoxicity, we identified a gut bacterial metabolite that controls the hepatic expression of CYP2E1 that catalyzes the conversion of APAP to a reactive, toxic metabolite. By comparing C57BL/6 substrain mice from two different vendors, Jackson (6J) and Taconic (6N), which are genetically similar but harbor different gut microbiotas, we established that the differences in the gut microbiotas result in differential susceptibility to APAP-induced hepatotoxicity. 6J mice exhibited lower susceptibility to APAP-induced hepatotoxicity than 6N mice, and such phenotypic difference was recapitulated in germ-free mice by microbiota transplantation. Comparative untargeted metabolomic analysis of portal vein sera and liver tissues between conventional and conventionalized 6J and 6N mice led to the identification of phenylpropionic acid (PPA), the levels of which were higher in 6J mice. PPA supplementation alleviated APAP-induced hepatotoxicity in 6N mice by lowering hepatic CYP2E1 levels. Moreover, PPA supplementation also reduced carbon tetrachloride-induced liver injury mediated by CYP2E1. Our data showed that previously known PPA biosynthetic pathway is responsible for PPA production. Surprisingly, while PPA in 6N mouse cecum contents is almost undetectable, 6N cecal microbiota produces PPA as well as 6J cecal microbiota
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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.