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Volume 15
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Review

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

by
Eugenio Caradonna
1,*,
Federico Abate
2,
Elisabetta Schiano
3,
Francesca Paparella
1,
Fulvio Ferrara
1,
Emilio Vanoli
4,
Rossana Difruscolo
5,
Vito Maria Goffredo
6,
Bruno Amato
7,
Carlo Setacci
8,
Francesco Setacci
9 and
Ettore Novellino
10
1
Integrated Laboratory Medicine Services, Centro Diagnostico Italiano S.p.A., 20011 Milan, Italy
2
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Via Vivaldi 43, 81100 Caserta, Italy
3
Inventia Biotech-Healthcare Food Research Center S.r.l., Strada Statale Sannitica KM 20.700, 81020 Caserta, Italy
4
School of Nursing, Cardiovascular Diseases, University of Pavia, 27100 Pavia, Italy
5
Faculty of Medicine, University of Bari, 70121 Bari, Italy
6
Department of Interdisciplinary Medicine, Università Degli Studi di Bari, 70124 Bari, Italy
7
Department of Public Health, Università Degli Studi di Napoli Federico II, 80138 Naples, Italy
8
Vascular and Endovascuar Surgery Unit, “Le Scotte” Hospital of Siena, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
9
Vascular Surgery Unit, Università degli Studi di Enna “Kore”, 94100 Enna, Italy
10
Department of Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
Metabolites 2025, 15(4), 220; https://doi.org/10.3390/metabo15040220
Submission received: 27 February 2025 / Revised: 18 March 2025 / Accepted: 19 March 2025 / Published: 24 March 2025
(This article belongs to the Special Issue Metabolism of Bioactives and Natural Products)
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Abstract

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.
Keywords: trimethylamine-N-oxide (TMAO); gut microbiota; cardiovascular diseases; atherosclerosis; endothelial dysfunction; neurodegenerative diseases trimethylamine-N-oxide (TMAO); gut microbiota; cardiovascular diseases; atherosclerosis; endothelial dysfunction; neurodegenerative diseases

Share and Cite

MDPI and ACS Style

Caradonna, E.; Abate, F.; Schiano, E.; Paparella, F.; Ferrara, F.; Vanoli, E.; Difruscolo, R.; Goffredo, V.M.; Amato, B.; Setacci, C.; et al. Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health. Metabolites 2025, 15, 220. https://doi.org/10.3390/metabo15040220

AMA Style

Caradonna E, Abate F, Schiano E, Paparella F, Ferrara F, Vanoli E, Difruscolo R, Goffredo VM, Amato B, Setacci C, et al. Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health. Metabolites. 2025; 15(4):220. https://doi.org/10.3390/metabo15040220

Chicago/Turabian Style

Caradonna, Eugenio, Federico Abate, Elisabetta Schiano, Francesca Paparella, Fulvio Ferrara, Emilio Vanoli, Rossana Difruscolo, Vito Maria Goffredo, Bruno Amato, Carlo Setacci, and et al. 2025. "Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health" Metabolites 15, no. 4: 220. https://doi.org/10.3390/metabo15040220

APA Style

Caradonna, E., Abate, F., Schiano, E., Paparella, F., Ferrara, F., Vanoli, E., Difruscolo, R., Goffredo, V. M., Amato, B., Setacci, C., Setacci, F., & Novellino, E. (2025). Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health. Metabolites, 15(4), 220. https://doi.org/10.3390/metabo15040220

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