ArticleProceedings of the National Academy of Sciences of the United States of America2012
Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 408 papers, 4 of them syntheses that pooled it.
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.
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Who cites it
408 citing papers in PubMed, 4 syntheses or guidelines pooled it, 682 citations in OpenAlex.
- The microbiota-gut-brain-epigenome axis as a novel therapeutic target for decoding postpartum depression.Frontiers in medicine · 2026Pooled it
- The microbiome-derived metabolite trimethylamine N-oxide is associated with chronic kidney disease risk.Applied microbiology and biotechnology · 2025Pooled it
- Impacts of intestinal microbiota metabolite trimethylamine N-oxide on cardiovascular disease: a bibliometric analysis.Frontiers in microbiology · 2024Pooled it
- Gut microbiota-derived metabolite trimethylamine-N-oxide and stroke outcome: a systematic review.Frontiers in molecular neuroscience · 2023Pooled it
- Trial
- Effect of dietary fiber on trimethylamine-N-oxide production after beef consumption and on gut microbiota: MEATMARK - a randomized cross-over study.European journal of clinical nutrition · 2025Trial
- Effect of acarbose and vildagliptin on plasma trimethylamine N-oxide levels in patients with type 2 diabetes mellitus: a 6-month, two-arm randomized controlled trial.Frontiers in endocrinology · 2025Trial
- Fecal Microbiome Composition Does Not Predict Diet-Induced TMAO Production in Healthy Adults.Journal of the American Heart Association · 2021Trial
- Gut microbiota and diet in colorectal cancer: Converging determinants of carcinogenesis.Gut microbes · 2026Review
- Sex differences in the gut microbiome and related metabolites: role in cardiometabolic disease.Gut microbes · 2026Review
- Cardiovascular-kidney-metabolic syndrome through the lens of gut‑derived uremic toxins.Gut microbes · 2026Review
- Trimethylamine-N-oxide: the microbial cue in immune-mediated disorders.Trends in endocrinology and metabolism: TEM · 2026Review
- Trained Immunity as a Mechanistic Bridge Between Uremic Toxins, Atherosclerosis, and Vascular Calcification in Chronic Kidney Disease.Cardiovascular toxicology · 2026Review
- Nutritional Modulation of the Gut Microbiome-Metabolite Axis in Cardiovascular Disease: From Dietary Patterns to Cardiovascular Risk.Current nutrition reports · 2026Review
- Transferable genetic toolsets for nonmodel gut Clostridia enable in vivo reversible control of metabolite production.Nature biotechnology · 2026Article
- Article
- Rhein alleviates acute pancreatitis by inhibiting TMAO-mediated inflammatory signaling pathways and reducing acinar cell injury.Journal of advanced research · 2026Article
- The microbiome regulates host metabolic health and diseases through microbial enzymes.Nature reviews. Gastroenterology & hepatology · 2026Review
- Integrating host-microbiome multi-omics with machine learning: methods, benchmarks, and translational applications.Science China. Life sciences · 2026Review
- Gut bacteria associated with an atherogenic TMAO-dietary pattern and choline-rich foods among aging women.Nutrition, metabolism, and cardiovascular diseases : NMCD · 2026Article
348 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Choline and trimethylamine (TMA) are small molecules that play central roles in biological processes throughout all kingdoms of life. These ubiquitous metabolites are linked through a single biochemical transformation, the conversion of choline to TMA by anaerobic microorganisms. This metabolic activity, which contributes to methanogenesis and human disease, has been known for over a century but has eluded genetic and biochemical characterization. We have identified a gene cluster responsible for anaerobic choline degradation within the genome of a sulfate-reducing bacterium and verified its function using both a genetic knockout strategy and heterologous expression in Escherichia coli. Bioinformatics and electron paramagnetic resonance (EPR) spectroscopy revealed the involvement of a C-N bond cleaving glycyl radical enzyme in TMA production, which is unprecedented chemistry for this enzyme family. Our discovery provides the predictive capabilities needed to identify choline utilization clusters in numerous bacterial genomes, underscoring the importance and prevalence of this metabolic activity within the human microbiota and the environment.
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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.