ArticleAlcohol, clinical & experimental research2023
Engineered bacteria producing aryl-hydrocarbon receptor agonists protect against ethanol-induced liver disease in mice.
Article in Alcohol, clinical & experimental research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Influence of Alcohol on the Intestinal Immune System.Alcohol research : current reviews · 2025Pooled it
- Perioperative gut microbial ecology: a new frontier for improving the prognosis of hepatocellular carcinoma surgery.Precision clinical medicine · 2026Review
- Maternal and infant gut microbiome.iMeta · 2026Review
- Gut-liver axis molecular mechanisms in alcohol-associated liver disease.Alcohol (Fayetteville, N.Y.) · 2026Review
- Gut microbiota-derived metabolites as immune modulators in aging and age-related chronic inflammatory diseases.Ageing research reviews · 2026Review
- An Update on IL-22 Therapies in Alcohol-Associated Liver Disease and Beyond.The American journal of pathology · 2026Review
- Microbiome-Driven Mechanisms in Breast Cancer: Emerging Evidence From Gut Microbial Signatures to Therapeutic Response.BioMed research international · 2026Review
- Reprogramming offspring liver health: maternal indole supplementation as a preventive strategy against MASLD.EBioMedicine · 2026Article
- Gut microbial metabolites of amino acids in liver diseases.Gut microbes · 2025Review
- Review
- Compositional and Metabolomic Shifts of the Gut Microbiome in Alcohol-Related Liver Disease.Journal of gastroenterology and hepatology · 2025Review
- Gut microbiome-specific nanoparticle-based therapeutics for liver diseases.World journal of gastroenterology · 2025Review
- Role of Intestinal Microbiome in Potentiating Inflammation and Predicting Outcomes in Alcohol-Associated Cirrhosis.Gastroenterology clinics of North America · 2025Review
- Impact of Gut Microbiome on Gut Permeability in Liver and Gut Diseases.Microorganisms · 2025Review
- Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer.Clinical and molecular hepatology · 2025Review
- Gut-X axis.iMeta · 2025Review
- Indole-3-Lactic Acid Inhibits Doxorubicin-Induced Ferroptosis Through Activating Aryl Hydrocarbon Receptor/Nrf2 Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Immunology and treatments of fatty liver disease.Archives of toxicology · 2025Review
- Immunomodulatory role of gut microbial metabolites: mechanistic insights and therapeutic frontiers.Frontiers in microbiology · 2025Review
- Gut Bacteria in Alcohol-Associated Liver Disease.Clinics in liver disease · 2024Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
background and purposeGut bacteria metabolize tryptophan into indoles. Intestinal levels of the tryptophan metabolite indole-3-acetic acid are reduced in patients with alcohol-associated hepatitis. Supplementation of indole-3-acetic acid protects against ethanol-induced liver disease in mice. The aim of this study was to evaluate the effect of engineered bacteria producing indoles as Aryl-hydrocarbon receptor (Ahr) agonists.
methodsC57BL/6 mice were subjected to chronic-plus-binge ethanol feeding and orally given PBS, control Escherichia coli Nissle 1917 (EcN) or engineered EcN-Ahr. The effects of EcN and EcN-Ahr were also examined in mice lacking Ahr in interleukin 22 (Il22)-producing cells.
resultsThrough the deletion of endogenous genes trpR and tnaA, coupled with overexpression of a feedback-resistant tryptophan biosynthesis operon, EcN-Ahr were engineered to overproduce tryptophan. Additional engineering allowed conversion of this tryptophan to indoles including indole-3-acetic acid and indole-3-lactic acid. EcN-Ahr ameliorated ethanol-induced liver disease in C57BL/6 mice. EcN-Ahr upregulated intestinal gene expression of Cyp1a1, Nrf2, Il22, Reg3b, and Reg3g, and increased Il22-expressing type 3 innate lymphoid cells. In addition, EcN-Ahr reduced translocation of bacteria to the liver. The beneficial effect of EcN-Ahr was abrogated in mice lacking Ahr expression in Il22-producing immune cells.
conclusionsOur findings indicate that tryptophan metabolites locally produced by engineered gut bacteria mitigate liver disease via Ahr-mediated activation in intestinal immune cells.
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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.