ArticleeLife2022
Gut microbial trimethylamine is elevated in alcohol-associated hepatitis and contributes to ethanol-induced liver injury in mice.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 53 citations in OpenAlex.
- Application of metabolomics in drug-induced liver injury: A systematic review.Journal of translational internal medicine · 2026Article
- Integrated multi-omic analyses reveal novel gene-metabolite relationships in human steatohepatitic hepatocellular carcinoma.Journal of lipid research · 2026Article
- Gut-liver axis molecular mechanisms in alcohol-associated liver disease.Alcohol (Fayetteville, N.Y.) · 2026Review
- Effects of alcohol use on the gut, inflammation, and organ injury: A summary of the 2025 Alcohol and Immunology Research Interest Group (AIRIG) meeting.Alcohol (Fayetteville, N.Y.) · 2026Article
- Gut microbe-derived trimethylamine shapes circadian rhythms through the host receptor TAAR5.eLife · 2026Article
- Classification of intestinal inflammation driven by gut microbiota metabolites: a new paradigm for precision treatment of cardiovascular diseases.Frontiers in microbiology · 2026Review
- The gut-liver-immune axis: structural basis, cellular architecture, molecular mediators, and disease-specific manifestations.Frontiers in immunology · 2026Review
- Review
- Gut Microbe-Derived Trimethylamine Shapes Circadian Rhythms Through the Host Receptor TAAR5.bioRxiv : the preprint server for biology · 2025Article
- Hepatic Inactivation of Carnitine Palmitoyltransferase 1a Lowers ApoB-Containing Lipoproteins in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Ferroptosis and gut microbiota: A new horizon in alcohol-associated liver disease management.Cellular and molecular life sciences : CMLS · 2025Review
- Role of Intestinal Microbiome in Potentiating Inflammation and Predicting Outcomes in Alcohol-Associated Cirrhosis.Gastroenterology clinics of North America · 2025Review
- Research progress in the role of gut microbiota in ethanol metabolism.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Immunology and treatments of fatty liver disease.Archives of toxicology · 2025Review
- Gut Microbiota as Emerging Players in the Development of Alcohol-Related Liver Disease.Biomedicines · 2024Review
- Alcohol-induced gut microbial reorganization and associated overproduction of phenylacetylglutamine promotes cardiovascular disease.Nature communications · 2024Article
- NLRP3 activation maintains intestinal epithelial barrier and reduces liver injury in alcoholic liver disease mice.Clinical and translational medicine · 2024Article
- Gut-liver axis: Recent concepts in pathophysiology in alcohol-associated liver disease.Hepatology (Baltimore, Md.) · 2024Review
- The pyruvate dehydrogenase kinase inhibitor dichloroacetate mitigates alcohol-induced hepatic inflammation and metabolic disturbances in mice.Hepatology communications · 2024Article
- Exploring Trimethylaminuria: Genetics and Molecular Mechanisms, Epidemiology, and Emerging Therapeutic Strategies.Biology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
36 authors at 8 institutions in 2 countries.
Funding
Abstract
There is mounting evidence that microbes residing in the human intestine contribute to diverse alcohol-associated liver diseases (ALD) including the most deadly form known as alcohol-associated hepatitis (AH). However, mechanisms by which gut microbes synergize with excessive alcohol intake to promote liver injury are poorly understood. Furthermore, whether drugs that selectively target gut microbial metabolism can improve ALD has never been tested. We used liquid chromatography tandem mass spectrometry to quantify the levels of microbe and host choline co-metabolites in healthy controls and AH patients, finding elevated levels of the microbial metabolite trimethylamine (TMA) in AH. In subsequent studies, we treated mice with non-lethal bacterial choline TMA lyase (CutC/D) inhibitors to blunt gut microbe-dependent production of TMA in the context of chronic ethanol administration. Indices of liver injury were quantified by complementary RNA sequencing, biochemical, and histological approaches. In addition, we examined the impact of ethanol consumption and TMA lyase inhibition on gut microbiome structure via 16S rRNA sequencing. We show the gut microbial choline metabolite TMA is elevated in AH patients and correlates with reduced hepatic expression of the TMA oxygenase flavin-containing monooxygenase 3 (FMO3). Provocatively, we find that small molecule inhibition of gut microbial CutC/D activity protects mice from ethanol-induced liver injury. CutC/D inhibitor-driven improvement in ethanol-induced liver injury is associated with distinct reorganization of the gut microbiome and host liver transcriptome. The microbial metabolite TMA is elevated in patients with AH, and inhibition of TMA production from gut microbes can protect mice from ethanol-induced liver injury.
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.