Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke
Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite, the production of which in vivo is mainly regulated by dietary choices, gut microbiota, and the hepatic enzyme flavin monooxygenase (FMO), while its elimination occurs via the kidneys. The TMAO level is positively correlated with...
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MDPI AG
2024-11-01
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| author | Zhen Li Xinyi He Qi Fang Xulong Yin |
| author_facet | Zhen Li Xinyi He Qi Fang Xulong Yin |
| author_sort | Zhen Li |
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| description | Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite, the production of which in vivo is mainly regulated by dietary choices, gut microbiota, and the hepatic enzyme flavin monooxygenase (FMO), while its elimination occurs via the kidneys. The TMAO level is positively correlated with the risk of developing cardiovascular diseases. Recent studies have found that TMAO plays an important role in the development of ischemic stroke. In this review, we describe the relationship between TMAO and ischemic stroke risk factors (hypertension, diabetes, atrial fibrillation, atherosclerosis, thrombosis, etc.), disease risk, severity, prognostic outcomes, and recurrence and discuss the possible mechanisms by which they interact. Importantly, TMAO induces atherosclerosis and thrombosis through lipid metabolism, foam cell formation, endothelial dysfunction (via inflammation, oxidative stress, and pyroptosis), enhanced platelet hyper-reactivity, and the upregulation and activation of vascular endothelial tissue factors. Although the pathogenic mechanisms underlying TMAO’s aggravation of disease severity and its effects on post-stroke neurological recovery and recurrence risk remain unclear, they may involve inflammation, astrocyte function, and pro-inflammatory monocytes. In addition, this paper provides a summary and evaluation of relevant preclinical and clinical studies on interventions regarding the gut-microbiota-dependent TMAO level to provide evidence for the prevention and treatment of ischemic stroke through the gut microbe–TMAO pathway. |
| format | Article |
| id | doaj-art-d5ce86b1672e4d2ab1a51eb60ba015b1 |
| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-11-01 |
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| series | Biomolecules |
| spelling | doaj-art-d5ce86b1672e4d2ab1a51eb60ba015b12025-08-20T02:28:11ZengMDPI AGBiomolecules2218-273X2024-11-011411146310.3390/biom14111463Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic StrokeZhen Li0Xinyi He1Qi Fang2Xulong Yin3Department of Neurology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215006, ChinaDepartment of Neurology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215006, ChinaDepartment of Neurology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215006, ChinaDepartment of Neurology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215006, ChinaTrimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite, the production of which in vivo is mainly regulated by dietary choices, gut microbiota, and the hepatic enzyme flavin monooxygenase (FMO), while its elimination occurs via the kidneys. The TMAO level is positively correlated with the risk of developing cardiovascular diseases. Recent studies have found that TMAO plays an important role in the development of ischemic stroke. In this review, we describe the relationship between TMAO and ischemic stroke risk factors (hypertension, diabetes, atrial fibrillation, atherosclerosis, thrombosis, etc.), disease risk, severity, prognostic outcomes, and recurrence and discuss the possible mechanisms by which they interact. Importantly, TMAO induces atherosclerosis and thrombosis through lipid metabolism, foam cell formation, endothelial dysfunction (via inflammation, oxidative stress, and pyroptosis), enhanced platelet hyper-reactivity, and the upregulation and activation of vascular endothelial tissue factors. Although the pathogenic mechanisms underlying TMAO’s aggravation of disease severity and its effects on post-stroke neurological recovery and recurrence risk remain unclear, they may involve inflammation, astrocyte function, and pro-inflammatory monocytes. In addition, this paper provides a summary and evaluation of relevant preclinical and clinical studies on interventions regarding the gut-microbiota-dependent TMAO level to provide evidence for the prevention and treatment of ischemic stroke through the gut microbe–TMAO pathway.https://www.mdpi.com/2218-273X/14/11/1463trimethylamine-N-oxideischemic strokegut microbiotamechanismsinterventions |
| spellingShingle | Zhen Li Xinyi He Qi Fang Xulong Yin Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke Biomolecules trimethylamine-N-oxide ischemic stroke gut microbiota mechanisms interventions |
| title | Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke |
| title_full | Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke |
| title_fullStr | Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke |
| title_full_unstemmed | Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke |
| title_short | Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke |
| title_sort | gut microbe generated metabolite trimethylamine n oxide and ischemic stroke |
| topic | trimethylamine-N-oxide ischemic stroke gut microbiota mechanisms interventions |
| url | https://www.mdpi.com/2218-273X/14/11/1463 |
| work_keys_str_mv | AT zhenli gutmicrobegeneratedmetabolitetrimethylaminenoxideandischemicstroke AT xinyihe gutmicrobegeneratedmetabolitetrimethylaminenoxideandischemicstroke AT qifang gutmicrobegeneratedmetabolitetrimethylaminenoxideandischemicstroke AT xulongyin gutmicrobegeneratedmetabolitetrimethylaminenoxideandischemicstroke |