ArticleLaboratory investigation; a journal of technical methods and pathology2019
Gut microbe-derived metabolite trimethylamine N-oxide induces cardiac hypertrophy and fibrosis.
Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
144 citing papers in PubMed, 2 syntheses or guidelines pooled it, 208 citations in OpenAlex.
- Anti-Inflammatory, Antioxidant, Metabolic and Gut Microbiota Modulation Activities of Probiotic in Cardiac Remodeling Condition: Evidence from Systematic Study and Meta-Analysis of Randomized Controlled Trials.Probiotics and antimicrobial proteins · 2023Pooled it
- Trimethylamine N-Oxide in Heart Failure: A Meta-Analysis of Prognostic Value.Frontiers in cardiovascular medicine · 2022Pooled it
- Probiotics Supplementation on Cardiac Remodeling Following Myocardial Infarction: a Single-Center Double-Blind Clinical Study.Journal of cardiovascular translational research · 2021Trial
- Alteration of gut microbiota contributes to peritoneal fibrosis through increased production of trimethylamine N-oxide.Gut microbes · 2026Article
- Trimethylamine N-oxide activates cardiac fibroblasts transformation through NLRP3 inflammasome activation with changes in mitochondrial dynamics and ER-mitochondrial contact under ER stress.Molecular and cellular biochemistry · 2026Article
- Cardiac fibroblast diversity in HFpEF: states, niches, interorgan drivers and targets.Nature reviews. Cardiology · 2026Review
- Clonal Hematopoiesis and Gut Microbiota-Derived TMAO as Candidate Amplifiers of Cardiovascular Inflammation: The CHIDT Hypothesis.Antioxidants (Basel, Switzerland) · 2026Review
- Targeting the Gut-Heart Axis in Diabetic Heart Failure: Microbiota and SGLT2is as Converging Therapeutic Frontiers.International journal of molecular sciences · 2026Review
- The cardioprotective mechanism of total saponins from mountain cultivated ginseng against doxorubicin-induced heart failure: Insights from gut-heart axis modulation based on gut microbiota and fecal metabolomics.Journal of ginseng research · 2026Article
- The impact of inflammation, neuromodulation, and gut microbiota on developing cardiac fibrosis and hypertension.Cardiovascular research · 2026Review
- Antibody-conjugated SIS3-loaded PLGA@polydopamine nanoparticles alleviate cardiac fibrosis by modulating Smad3 signaling in myofibroblasts.Journal of nanobiotechnology · 2026Article
- Metabolic syndrome and a broken heart: trust your gut or risk your heart.American journal of physiology. Heart and circulatory physiology · 2026Review
- The Heart-Gut Axis in Heart Failure: The Role of Next-Generation Pharmacological Therapies.International journal of molecular sciences · 2026Review
- Exploring the basis of Traditional Chinese Medicine in treating cardiovascular disease: insights into the microbiota-gut-heart axis.Chinese medicine · 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
- Gut Microbiota-Derived Metabolite and Heart Failure with Reduced Ejection Fraction (HFrEF): Elevated Trimethylamine N-Oxide (TMAO) as a Potential Biomarker.International journal of molecular sciences · 2026Article
- Classification of intestinal inflammation driven by gut microbiota metabolites: a new paradigm for precision treatment of cardiovascular diseases.Frontiers in microbiology · 2026Review
- The role of gut microbiome disruption in the development of metabolic dysfunction-associated kidney disease.Acta biochimica Polonica · 2026Review
- Gut-heart axis at high altitude: a dynamic mediator from hypoxic dysbiosis to adaptive cardioprotection.Frontiers in microbiology · 2026Review
84 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trimethylamine N-oxide (TMAO), a gut microbe-derived metabolite of dietary choline and other trimethylamine-containing nutrients, has been linked to increased cardiovascular disease risk. It is unknown whether TMAO plays a role in the development of cardiac hypertrophy. Transverse aortic constriction (TAC) was performed to induce cardiac hypertrophy in Sprague-Dawley (SD) rats. We observed that TMAO levels were significantly elevated in SD rats after 6 weeks of TAC, suggesting the potential role of TMAO in regulating cardiac hypertrophy. In cultured cardiomyocytes, TMAO treatment stimulated cardiac hypertrophy, as indicated by increased cell area of cardiomyocytes and expression of hypertrophic markers including atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). Additionally, TMAO treatment induced cardiac hypertrophy and cardiac fibrosis in SD rats. Reducing TMAO synthesis by antibiotics (Abs) attenuated TAC-induced cardiac hypertrophy and fibrosis. Furthermore, pharmacological inhibition of Smad3 by SIS3 significantly reduced the expression of ANP and β-MHC, and cardiomyocyte cell size in TMAO-treated group. These data for the first time demonstrate that gut microbe-derived metabolite TMAO induces cardiac hypertrophy and fibrosis involving Smad3 signaling, suggesting that inhibition of gut microbes or generation of TMAO may become a potential target for the prevention and treatment of cardiac hypertrophy.
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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.