TMAO at the Crossroads of the Gut–Brain Axis: Emerging Mechanisms Linking Microbiota-Derived Metabolites to Neuroinflammation and Cognitive Dysfunction
- 1Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Toledo, OH 43614, USA
- 2Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Toledo, OH 43614, USA
Abstract
Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite produced through the hepatic oxidation of trimethylamine. Although TMAO has been widely investigated as a therapeutic target in multiple cardiovascular and metabolic diseases, growing evidence suggests it may play a critical role in the neuroinflammation and cognitive dysfunction associated with the gut–brain axis. This narrative review summarizes the current literature to synthesize evidence on the mechanisms linking TMAO with neurological disorders; it discusses potential mechanisms contributing to this association, with particular focus on neuroinflammation, oxidative stress, and activation of inflammatory pathways. Overall, this review also suggests the potential use of TMAO and its precursors as therapeutic targets for multiple neurodegenerative disorders. However, it emphasizes the need for conducting large, adequately powered randomized clinical studies to determine its therapeutic relevance.
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BibTeX
@article{altahrawi2026tmao,
title = {{TMAO at the Crossroads of the Gut–Brain Axis: Emerging Mechanisms Linking Microbiota-Derived Metabolites to Neuroinflammation and Cognitive Dysfunction}},
author = {Aseel Y. Altahrawi and Fatimah Sofi and Zara Kanjwal and Zahoor A. Shah},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15201845},
url = {https://www.mdpi.com/2073-4409/15/20/1845},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - TMAO at the Crossroads of the Gut–Brain Axis: Emerging Mechanisms Linking Microbiota-Derived Metabolites to Neuroinflammation and Cognitive Dysfunction
AU - Aseel Y. Altahrawi
AU - Fatimah Sofi
AU - Zara Kanjwal
AU - Zahoor A. Shah
PY - 2026
DA - 2026/10/12
JO - Cells
DO - 10.3390/cells15201845
UR - https://www.mdpi.com/2073-4409/15/20/1845
AB - Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite produced through the hepatic oxidation of trimethylamine. Although TMAO has been widely investigated as a therapeutic target in multiple cardiovascular and metabolic diseases, growing evidence suggests it may play a critical role in the neuroinflammation and cognitive dysfunction associated with the gut–brain axis. This narrative review summarizes the current literature to synthesize evidence on the mechanisms linking TMAO with neurological disorders; it discusses potential mechanisms contributing to this association, with particular focus on neuroinflammation, oxidative stress, and activation of inflammatory pathways. Overall, this review also suggests the potential use of TMAO and its precursors as therapeutic targets for multiple neurodegenerative disorders. However, it emphasizes the need for conducting large, adequately powered randomized clinical studies to determine its therapeutic relevance.
SN - 2073-4409
ER -