Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health

The intestinal microbiota, hosting trillions of microorganisms that inhabit the gastrointestinal tract, functions as a symbiotic organism that plays a crucial role in regulating health by producing biologically active molecules that can enter systemic circulation. Among them, trimethylamine-N-oxide...

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Main Authors: Eugenio Caradonna, Federico Abate, Elisabetta Schiano, Francesca Paparella, Fulvio Ferrara, Emilio Vanoli, Rossana Difruscolo, Vito Maria Goffredo, Bruno Amato, Carlo Setacci, Francesco Setacci, Ettore Novellino
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Language:English
Published: MDPI AG 2025-03-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/15/4/220
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author Eugenio Caradonna
Federico Abate
Elisabetta Schiano
Francesca Paparella
Fulvio Ferrara
Emilio Vanoli
Rossana Difruscolo
Vito Maria Goffredo
Bruno Amato
Carlo Setacci
Francesco Setacci
Ettore Novellino
author_facet Eugenio Caradonna
Federico Abate
Elisabetta Schiano
Francesca Paparella
Fulvio Ferrara
Emilio Vanoli
Rossana Difruscolo
Vito Maria Goffredo
Bruno Amato
Carlo Setacci
Francesco Setacci
Ettore Novellino
author_sort Eugenio Caradonna
collection DOAJ
description The intestinal microbiota, hosting trillions of microorganisms that inhabit the gastrointestinal tract, functions as a symbiotic organism that plays a crucial role in regulating health by producing biologically active molecules that can enter systemic circulation. Among them, trimethylamine-N-oxide (TMAO), an organic compound derived from dietary sources and microbial metabolism, has emerged as a critical biomarker linking diet, the gut microbiota, and the host metabolism to various pathological conditions. This comprehensive review highlights TMAO’s biosynthesis, physiological functions, and clinical significance, focusing on its mechanistic contributions to cardiovascular and neurodegenerative diseases. Notably, TMAO-mediated pathways include endothelial dysfunction, inflammation via NLRP3 inflammasome activation, and cholesterol metabolism disruption, which collectively accelerate atherosclerosis and disease progression. Nonetheless, this work underscores the innovative potential of targeting TMAO through dietary, nutraceutical, and microbiota-modulating strategies to mitigate its pathological effects, marking a transformative approach in the prevention and management of TMAO-related disorders.
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spelling doaj-art-e92b0d42ec2942df969910debe3407a82025-08-20T03:13:45ZengMDPI AGMetabolites2218-19892025-03-0115422010.3390/metabo15040220Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human HealthEugenio Caradonna0Federico Abate1Elisabetta Schiano2Francesca Paparella3Fulvio Ferrara4Emilio Vanoli5Rossana Difruscolo6Vito Maria Goffredo7Bruno Amato8Carlo Setacci9Francesco Setacci10Ettore Novellino11Integrated Laboratory Medicine Services, Centro Diagnostico Italiano S.p.A., 20011 Milan, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Via Vivaldi 43, 81100 Caserta, ItalyInventia Biotech-Healthcare Food Research Center S.r.l., Strada Statale Sannitica KM 20.700, 81020 Caserta, ItalyIntegrated Laboratory Medicine Services, Centro Diagnostico Italiano S.p.A., 20011 Milan, ItalyIntegrated Laboratory Medicine Services, Centro Diagnostico Italiano S.p.A., 20011 Milan, ItalySchool of Nursing, Cardiovascular Diseases, University of Pavia, 27100 Pavia, ItalyFaculty of Medicine, University of Bari, 70121 Bari, ItalyDepartment of Interdisciplinary Medicine, Università Degli Studi di Bari, 70124 Bari, ItalyDepartment of Public Health, Università Degli Studi di Napoli Federico II, 80138 Naples, ItalyVascular and Endovascuar Surgery Unit, “Le Scotte” Hospital of Siena, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, ItalyVascular Surgery Unit, Università degli Studi di Enna “Kore”, 94100 Enna, ItalyDepartment of Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, ItalyThe intestinal microbiota, hosting trillions of microorganisms that inhabit the gastrointestinal tract, functions as a symbiotic organism that plays a crucial role in regulating health by producing biologically active molecules that can enter systemic circulation. Among them, trimethylamine-N-oxide (TMAO), an organic compound derived from dietary sources and microbial metabolism, has emerged as a critical biomarker linking diet, the gut microbiota, and the host metabolism to various pathological conditions. This comprehensive review highlights TMAO’s biosynthesis, physiological functions, and clinical significance, focusing on its mechanistic contributions to cardiovascular and neurodegenerative diseases. Notably, TMAO-mediated pathways include endothelial dysfunction, inflammation via NLRP3 inflammasome activation, and cholesterol metabolism disruption, which collectively accelerate atherosclerosis and disease progression. Nonetheless, this work underscores the innovative potential of targeting TMAO through dietary, nutraceutical, and microbiota-modulating strategies to mitigate its pathological effects, marking a transformative approach in the prevention and management of TMAO-related disorders.https://www.mdpi.com/2218-1989/15/4/220trimethylamine-N-oxide (TMAO)gut microbiotacardiovascular diseasesatherosclerosisendothelial dysfunctionneurodegenerative diseases
spellingShingle Eugenio Caradonna
Federico Abate
Elisabetta Schiano
Francesca Paparella
Fulvio Ferrara
Emilio Vanoli
Rossana Difruscolo
Vito Maria Goffredo
Bruno Amato
Carlo Setacci
Francesco Setacci
Ettore Novellino
Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health
Metabolites
trimethylamine-N-oxide (TMAO)
gut microbiota
cardiovascular diseases
atherosclerosis
endothelial dysfunction
neurodegenerative diseases
title Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health
title_full Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health
title_fullStr Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health
title_full_unstemmed Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health
title_short Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health
title_sort trimethylamine n oxide tmao as a rising star metabolite implications for human health
topic trimethylamine-N-oxide (TMAO)
gut microbiota
cardiovascular diseases
atherosclerosis
endothelial dysfunction
neurodegenerative diseases
url https://www.mdpi.com/2218-1989/15/4/220
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