Trimethylamine-N-oxide: a potential biomarker and therapeutic target in ischemic stroke

Liu, Yuan; Qu, Juan; Xu, Jing; Gu, Aiming; Deng, Dezhi; Wang, Baoxiang

doi:10.3389/fneur.2023.1156879

Cited by 3 publications

(2 citation statements)

References 70 publications

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“…In contrast to circulating choline, we did not find an association between plasma TMAO levels and CVD risk or mortality in our population‐based cohorts. Even though a number of studies have shown a relationship between TMAO levels and CVD risk, these results are mostly derived from individuals with a high risk of CVD, existing disease, or multimorbidity [ 6 , 7 , 8 , 43 , 44 , 45 , 46 ]. In line with our results, a few population‐based studies did not identify an association between TMAO and cardiometabolic markers, carotid intima media thickness, CVD events including heart attack and stroke and mortality, either [ 9 , 21 , 47 , 48 ], while some other studies did report significant associations [ 10 , 11 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

Unraveling interindividual variation of trimethylamine N‐oxide and its precursors at the population level

Andreu‐Sánchez,

Ahmad,

Kurilshikov

et al. 2024

iMeta

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Trimethylamine N‐oxide (TMAO) is a circulating microbiome‐derived metabolite implicated in the development of atherosclerosis and cardiovascular disease (CVD). We investigated whether plasma levels of TMAO, its precursors (betaine, carnitine, deoxycarnitine, choline), and TMAO‐to‐precursor ratios are associated with clinical outcomes, including CVD and mortality. This was followed by an in‐depth analysis of their genetic, gut microbial, and dietary determinants. The analyses were conducted in five Dutch prospective cohort studies including 7834 individuals. To further investigate association results, Mendelian Randomization (MR) was also explored. We found only plasma choline levels (hazard ratio [HR] 1.17, [95% CI 1.07; 1.28]) and not TMAO to be associated with CVD risk. Our association analyses uncovered 10 genome‐wide significant loci, including novel genomic regions for betaine (6p21.1, 6q25.3), choline (2q34, 5q31.1), and deoxycarnitine (10q21.2, 11p14.2) comprising several metabolic gene associations, for example, CPS1 or PEMT. Furthermore, our analyses uncovered 68 gut microbiota associations, mainly related to TMAO‐to‐precursors ratios and the Ruminococcaceae family, and 16 associations of food groups and metabolites including fish‐TMAO, meat‐carnitine, and plant‐based food‐betaine associations. No significant association was identified by the MR approach. Our analyses provide novel insights into the TMAO pathway, its determinants, and pathophysiological impact on the general population.

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Section: Discussionmentioning

confidence: 99%

Unraveling interindividual variation of trimethylamine N‐oxide and its precursors at the population level

Andreu‐Sánchez,

Ahmad,

Kurilshikov

et al. 2024

iMeta

View full text Add to dashboard Cite

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“…The gut microbiota and its metabolites may affect the risk factors of stroke, such as hypertension, obesity, and diabetes, or signal inflammation and immune responses during atherosclerosis and thrombosis . To be specific, a growing body of evidence suggests that Trimethylamine-N-oxide (TMAO), a small molecular compound derived from the metabolism of intestinal microorganisms, is associated with the elevated risk of stroke, as well as the severity and prognosis of stroke (Liu et al, 2023). Clinical evidence from dose-response meta-analyses also show the circulating TMAO is positively associated with an increased probability of risk factors in stroke, such as hypertension (Abbasalizad Farhangi and Vajdi, 2021), and inflammatory parameters involved in the pathological process of atherosclerosis, such as C-reactive protein (Farhangi and Vajdi, 2020).…”

Section: Introductionmentioning

confidence: 99%

The preliminary evidence on the association of the gut microbiota with stroke risk stratification in South Chinese population

Huang,

Kuang,

et al. 2023

Front. Cell. Infect. Microbiol.

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AimsThis study aimed to investigate the association between the gut microbiota and the risk of stroke.MethodsFaecal samples from 60 participants in South China, including 45 individuals with risk factors for stroke and 15 healthy controls, were collected and subjected to 16S rRNA sequencing. A bioinformatics analysis was performed to characterise the gut microbial diversity and taxonomic compositions at different risk levels (low, moderate, and high) of stroke. Functional prediction and correlation analyses between the microbiota and laboratory markers were performed to explore the potential mechanisms.ResultsA significant difference in beta diversity was observed between the participants from the stroke risk and healthy control groups. Linear discriminant effect size analysis revealed a large number of vascular beneficial bacteria enriched in the participants from the healthy control and low-risk groups, but a few vascular harmful bacteria were more abundant in the participants from the high-risk group than in those from the other groups. In addition, Anaerostipes, Clostridium_XlVb, and Flavonifractor, all of which belonged to the Firmicutes phylum, were enriched in the participants from the low-risk group, and their relative abundances gradually decreased as the stroke risk increased. Spearman’s analysis revealed that these outstanding microbiota correlated with the levels of triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, white blood cells, neutrophils, and carotid intima-media thickness.ConclusionThe preliminary evidence suggests that gut microbiota is associated with stroke risk. It potentially ameliorates atherosclerosis by targeting lipid metabolism and inflammation. This provides novel insights into the early screening of stroke risk and primary prevention.

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Identification of Urine Metabolic Markers of Stroke Risk Using Untargeted Nuclear Magnetic Resonance Analysis

Oliveira,

Sousa,

Amaral

et al. 2024

IJMS

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Stroke remains the second leading cause of mortality worldwide, and the third leading cause of death and morbidity combined, affecting more than 12 million people every year. Stroke pathophysiology results from complex interactions of several risk factors related to age, family history, gender, lifestyle, and the presence of cardiovascular and metabolic diseases. Despite all the evidence, it is not possible to fully prevent stroke onset. In recent years, there has been an exploration of innovative methodologies for metabolite analysis aimed at identifying novel stroke biomarkers. Utilizing Nuclear Magnetic Resonance (NMR) spectroscopy, we investigated small molecule variations in urine across different stages of stroke risk. The Framingham Stroke Risk Score was used in people over 63 years of age living in long-term care facilities (LTCFs) to calculate the probability of suffering a stroke: low stroke risk (LSR, control), moderate stroke risk (MSR), and high stroke risk (HSR). Univariate statistical analysis showed that urinary 4-hydroxyphenylacetate levels increased while glycolate levels decreased across the different stroke risk groups, from the LSR to the HSR groups. Trimethylamine N-oxide (TMAO) had average concentration values that were significantly higher in elderly people in the HSR group, while trigonelline levels were significantly lower in the MSR group. These metabolic markers can be used for early detection and to differentiate stages of stroke risk more efficiently.

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Trimethylamine-N-oxide: a potential biomarker and therapeutic target in ischemic stroke

Cited by 3 publications

References 70 publications

Unraveling interindividual variation of trimethylamine N‐oxide and its precursors at the population level

Unraveling interindividual variation of trimethylamine N‐oxide and its precursors at the population level

The preliminary evidence on the association of the gut microbiota with stroke risk stratification in South Chinese population

Identification of Urine Metabolic Markers of Stroke Risk Using Untargeted Nuclear Magnetic Resonance Analysis

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