ArticleNature medicine2018
Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04510324 (Plant-Based Meat vs Animal "Red" Meat), which is not on this map. Cited by 319 papers, 7 of them syntheses that pooled it.
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.
Plant-Based Meat vs Animal "Red" Meat: a Randomized Cross-over Trial
Who cites it
319 citing papers in PubMed, 7 syntheses or guidelines pooled it, 534 citations in OpenAlex.
- A systematic review of TMAO, microRNAs, and the oral/gut microbiomes in atherosclerosis and myocardial infarction: mechanistic insights and translational opportunities.Journal of translational medicine · 2025Pooled it
- Impacts of intestinal microbiota metabolite trimethylamine N-oxide on cardiovascular disease: a bibliometric analysis.Frontiers in microbiology · 2024Pooled it
- Clinical trials targeting the gut-microbiome to effect ocular health: a systematic review.Eye (London, England) · 2023Pooled it
- Meat Consumption and Gut Microbiota: a Scoping Review of Literature and Systematic Review of Randomized Controlled Trials in Adults.Advances in nutrition (Bethesda, Md.) · 2023Pooled it
- The relationship between trimethylamine-N-oxide and the risk of acute ischemic stroke: A dose‒response meta-analysis.PloS one · 2023Pooled it
- Benefits and Implications of Resveratrol Supplementation on Microbiota Modulations: A Systematic Review of the Literature.International journal of molecular sciences · 2022Pooled it
- Trimethylamine N-Oxide in Heart Failure: A Meta-Analysis of Prognostic Value.Frontiers in cardiovascular medicine · 2022Pooled it
- Processed plant-based meat-supplemented diet versus red meat-based supplemented diet randomized cross-over trial Finding Optimal Oral Diet-1 (FOOD-1) trial.Scientific reports · 2026Trial
- Gut Microbiota-Generated Phenylacetylglutamine and Heart Failure.Circulation. Heart failure · 2023Trial
- Cardiovascular-kidney-metabolic syndrome through the lens of gut‑derived uremic toxins.Gut microbes · 2026Review
- Review
- 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
- Gut microecology and cardiovascular disease: core pathogenic mechanisms and clinical intervention strategies.Folia microbiologica · 2026Review
- The TMAO Metabolic Axis in Vascular Disease: A Position Paper on Redox Mechanisms and Priorities for Clinical Translation.Antioxidants (Basel, Switzerland) · 2026Article
- From Fecal Microbial Potential to Circulating Trimethylamine N-oxide and Cardiovascular Events: A Narrative Review.Cureus · 2026Review
- Microbiome alterations and their potential impact on infection risk in chronic kidney disease and end-stage kidney disease: a narrative review.International urology and nephrology · 2026Review
- Gut microbial trimethylamine N-oxide generation promotes risk of atrial fibrillation via muscarinic receptor-mediated autonomic dysfunction.The Journal of clinical investigation · 2026Article
- Anaerobic riboflavin degradation by human gutJournal of bacteriology · 2026Article
- TMAO Correlates with Transcriptomic Signatures of Leukocyte Activation and Systemic Inflammation Following Burn Injury.Journal of burn care & research : official publication of the American Burn Association · 2026Article
259 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 5 institutions in 1 country.
Funding
Abstract
Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite that enhances both platelet responsiveness and in vivo thrombosis potential in animal models, and TMAO plasma levels predict incident atherothrombotic event risks in human clinical studies. TMAO is formed by gut microbe-dependent metabolism of trimethylamine (TMA) moiety-containing nutrients, which are abundant in a Western diet. Here, using a mechanism-based inhibitor approach targeting a major microbial TMA-generating enzyme pair, CutC and CutD (CutC/D), we developed inhibitors that are potent, time-dependent, and irreversible and that do not affect commensal viability. In animal models, a single oral dose of a CutC/D inhibitor significantly reduced plasma TMAO levels for up to 3 d and rescued diet-induced enhanced platelet responsiveness and thrombus formation, without observable toxicity or increased bleeding risk. The inhibitor selectively accumulated within intestinal microbes to millimolar levels, a concentration over 1-million-fold higher than needed for a therapeutic effect. These studies reveal that mechanism-based inhibition of gut microbial TMA and TMAO production reduces thrombosis potential, a critical adverse complication in heart disease. They also offer a generalizable approach for the selective nonlethal targeting of gut microbial enzymes linked to host disease limiting systemic exposure of the inhibitor in the host.
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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.