ArticleEBioMedicine2019
Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathways.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- Metabolic Signatures of Atrial Functional Impairment in Paroxysmal Atrial Fibrillation Patients: A CMR Strain-metabolomics Study.Journal of cardiovascular translational research · 2026Article
- Role of Exercise in Modulating the Brain-Heart Axis in Cardiovascular Diseases.International journal of molecular sciences · 2026Review
- Multi-Omics Mechanisms of Trimethylamine Oxide and Cardiovascular Disease: A Review.Reviews in cardiovascular medicine · 2026Review
- Gut Microbiota-Derived Trimethylamine N-Oxide and NT-proBNP in Heart Failure: A Critical Review of Diagnostic and Prognostic Value.Biomedicines · 2026Review
- Interplay between Skin Sympathetic Nerve Activity and Gut Microbiota, the Neurocardiac Axis in Acute Coronary Syndrome.International journal of medical sciences · 2026Article
- Enhanced Neuromodulation Using PC-CNTs and NIR Photothermal Therapy for Preventing Ventricular Arrhythmias.International journal of nanomedicine · 2026Article
- Blood metabolites mediate causal inference studies on the effect of gut microbiota on the risk of vascular calcification.Journal of advanced research · 2026Article
- Trimethylamine-N-oxide promotes fibrotic activation of quiescent valvular interstitial cells via endoplasmic reticulum stress.Scientific reports · 2025Article
- Interplay Among Gut Microbiota-Derived TMAO, Autonomic Nervous System Dysfunction, and Heart Failure Progression.International journal of molecular sciences · 2025Review
- Mechanisms of exercise in preventing cardiovascular diseases: Insights from gut microbiota characteristics in pathological states of cardiovascular diseases.Reviews in endocrine & metabolic disorders · 2025Review
- Gut microbiota and the tryptophan-kynurenine pathway in anxiety: new insights and treatment strategies.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- Potential role of gut microbiota in cardiac arrhythmias.American heart journal plus : cardiology research and practice · 2025Article
- The Gut Microbiome and Cardiac Arrhythmias.Federal practitioner : for the health care professionals of the VA, DoD, and PHS · 2025Review
- Short-chain fatty acid butyrate against TMAO activating endoplasmic-reticulum stress and PERK/IRE1-axis with reducing atrial arrhythmia.Journal of advanced research · 2025Article
- Targeted M-Channel Activation in the Left Stellate Ganglion Protects Against Ischemia-Induced Ventricular Arrhythmias in Canines.Journal of the American Heart Association · 2025Article
- Post-stroke Arrhythmias: Performance of Brain-heart Crosstalk Networks.Current cardiology reviews · 2025Review
- Gut microbiota metabolites and key target molecules in allergic rhinitis: a multi-omics study of gut-nose axis regulation via the inflammation-metabolism network.Frontiers in microbiology · 2025Article
- Mast cell stabilizer, an anti-allergic drug, reduces ventricular arrhythmia risk via modulation of neuroimmune interaction.Basic research in cardiology · 2024Article
- Targeting gut microbiota in aging-related cardiovascular dysfunction: focus on the mechanisms.Gut microbes · 2023Review
- The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases.Frontiers in endocrinology · 2023Review
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe previously demonstrated the gut microbes-derived metabolite trimethylamine N-oxide (TMAO) could activate the atrial autonomic ganglion plexus and promote atrial arrhythmia. The cardiac sympathetic nervous system (CSNS) play important roles in modulating ventricular arrhythmia (VA).
methodsPart 1: To test whether TMAO can directly activate the CSNS, we performed local injection of TMAO into the left stellate ganglion (LSG). Part 2: To test whether TMAO can indirectly activate the CSNS through the central nervous system, we performed intravenous injection of TMAO. Ventricular electrophysiology and LSG function and neural activity were measured before and after TMAO administration. Then, the left anterior descending coronary artery was ligated, and electrocardiograms were recorded for 1 h. At the end of the experiment, LSG and paraventricular nucleus (PVN) tissues were excised for molecular analyses.
findingsCompared with the control, both intravenous and local TMAO administration significantly increased LSG function and activity, shortened effective refractory period, and aggravated ischemia-induced VA. Proinflammatory markers and c-fos in the LSG were also significantly upregulated in both TMAO-treated groups. Particularly, c-fos expression in PVN was significantly increased in the systemic TMAO administration group but not the local TMAO administration group.
interpretationThe gut microbe-derived metabolite TMAO can activate the CSNS and aggravate ischemia-induced VA via the direct pathway through the LSG and the indirect pathway through central autonomic activation. FUND: This work was supported by the National Key R&D Program of China [2017YFC1307800], and the National Natural Science Foundation of China [81530011, 81770364, 81570463, 81871486, 81600395, 81600367 and 81700444].
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