ArticleNutrients2022
Gut-Flora-Dependent Metabolite Trimethylamine-N-Oxide Promotes Atherosclerosis-Associated Inflammation Responses by Indirect ROS Stimulation and Signaling Involving AMPK and SIRT1.
Article in Nutrients, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Gut microbiota regulate atherosclerosis via the gut-vascular axis: a scoping review of mechanisms and therapeutic interventions.Frontiers in microbiology · 2025Pooled it
- Review
- Review
- The Role of Anti-Inflammatory Nutrition in Metabolic Syndrome and Cardiometabolic Diseases.Nutrients · 2026Review
- Targeting the Gut-Heart Axis in Atherosclerosis: Microbial Metabolites, Molecular Mechanisms, and Precision Therapeutics.Probiotics and antimicrobial proteins · 2026Review
- [Mechanisms of gutZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- The gut-heart dialogue: an epigenetic perspective on myocardial infarction.NPJ biofilms and microbiomes · 2026Review
- Involvement of trimethylamine N-oxide in major depressive disorder via astrocytic d-Serine dysregulation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- SIRT1 in Atherosclerosis: Integrative Control of Vascular Metabolism, Inflammation and Aging.International journal of molecular sciences · 2026Review
- Article
- Legume intake on gut microbiome and glycemia in type 2 diabetes management: narrative review.Frontiers in nutrition · 2026Review
- Nutrition and the gut microbiome: a symbiotic dialogue influencing health and disease.Frontiers in nutrition · 2026Review
- Trimethylamine N-Oxide Linking Gut Microbiota to Cardiocerebral Disease Is a Novel Biomarker for Stroke Subtypes With Mixed Etiology: A Prospective Cohort Study.CNS neuroscience & therapeutics · 2025Article
- Trimethylamine-Annals of medicine · 2025Review
- SGLT2 Inhibitors Confer Cardiovascular Protection via the Gut-Kidney-Heart Axis: Mechanisms and Translational Perspectives.Journal of cardiovascular development and disease · 2025Review
- Dietary choline-derived Trimethylamine N-oxide impairs hippocampal neuronal function via PANoptosis activation.NPJ science of food · 2025Article
- Advances in Molecular Mechanisms and Precision Interventions of Cardiovascular Injuries Related to Glucose and Lipid Metabolism Disorders.Reviews in cardiovascular medicine · 2025Review
- The Oral-Gut Microbiota Axis Across the Lifespan: New Insights on a Forgotten Interaction.Nutrients · 2025Review
- The gut microbiota metabolite trimethylamine-N-oxide in children with β-thalassemia: potential implication for iron-induced renal tubular dysfunction.Pediatric research · 2025Article
- Gut microbiota-derived TMAO and SIRT1/HMGB1 Axis: unveiling mechanisms of renal impairment in beta-thalassemia major.Pediatric research · 2025Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Trimethylamine-N-oxide (TMAO), a gut-microbiota-dependent metabolite after ingesting dietary choline, has been identified as a novel risk factor for atherosclerosis through inducing vascular inflammation. However, the underlying molecular mechanism is poorly understood. Using an in vitro vascular cellular model, we found that the TMAO-induced inflammation responses were correlated with an elevation of ROS levels and downregulation of SIRT1 expression in VSMCs and HUVECs. The overexpression of SIRT1 could abrogate both the stimulation of ROS and inflammation. Further studies revealed that AMPK was also suppressed by TMAO and was a mediator upstream of SIRT1. Activation of AMPK by AICAR could reduce TMAO-induced ROS and inflammation. Moreover, the GSH precursor NAC could attenuate TMAO-induced inflammation. In vivo studies with mice models also showed that choline-induced production of TMAO and the associated glycolipid metabolic changes leading to atherosclerosis could be relieved by NAC and a probiotic LP8198. Collectively, the present study revealed an unrecognized mechanistic link between TMAO and atherosclerosis risk, and probiotics ameliorated TMAO-induced atherosclerosis through affecting the gut microbiota. Consistent with previous studies, our data confirmed that TMAO could stimulate inflammation by modulating cellular ROS levels. However, this was not due to direct cytotoxicity but through complex signaling pathways involving AMPK and SIRT1.
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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.