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Advanced Neurology TMAO and stroke

factors for IS primarily focus on uncontrollable factors promoting the development of atherosclerosis in vivo.
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such as age and genetics, as well as controllable factors It is noteworthy that participants with increased TMAO
like hypertension and diabetes. However, recent research quintile levels at baseline were characterized by mildly
have found that dietary habits and gut metabolites play a higher body mass index, blood pressure, triglycerides, and
significant role in the pathogenesis of IS. The discovery of fasting glucose, as well as a lower estimated glomerular
trimethylamine N-oxide (TMAO) offers a new perspective filtration rate. This may suggest the interaction between
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for understanding the complex relationship between gut TMAO and other cerebrovascular risk factors in the early
microbiota and diseases. TMAO, a gut metabolite that has stage.
been widely discussed in recent years, has been shown to be However, TMAO is not entirely devoid of advantages.
closely associated with the occurrence and development of TMAO not only participates in the regulation of oxidative
various diseases, including atherosclerosis, hypertension, reactions, osmotic reactions, and hydrostatic pressure
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and IS. This review aims to explore the mechanisms of but also regulates the activities of various enzymes and
TMAO in IS and its potential as a new target for prevention hormones, and plays a role in maintaining the stability
and treatment. With ongoing research on TMAO, there is of protein structures. In nature, urea and TMAO are
reason to believe that by adjusting dietary structures or sometimes found together in the same organism. The
exploring new intervention methods possible provide new combined effect of these compounds may protect the
insights into reducing the incidence of IS and improving lipid membrane from dehydration and prevent protein
patient outcomes.
denaturation. 10
2. Metabolism of TMAO 3. TMAO and stroke
Trimethylamine (TMA) is the primary source of TMA As the largest developing country in the world, China
N-oxide (TMAO), an important intestinal metabolite holds one-fifth of the global population and has the highest
that has been extensively studied because of its close number of stroke patients. At present, stroke has emerged
relationship to cardiovascular, renal, and other diseases. as the major cause of premature death and disease burden
Humans obtain TMA by consuming foods rich in among Chinese citizens. Research has linked the gut
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choline, L-carnitine, and phosphatidylcholine, including metabolite TMAO to high cholesterol levels, hypertension,
red meat, dairy products, fish, other seafood, and eggs. obesity, and atrial fibrillation. The strong association
Microorganisms metabolize TMA produced in the between TMAO and stroke is becoming more and more
intestinal circulation and absorb it into the systemic apparent as more research explores this issue. Large
circulation, where flavin monooxygenases (FMOs) in the pooled data indicate that ischemic stroke (IS) patients have
liver oxidize it to TMAO. The expression of FMO3 is the significantly higher levels of TMAO than healthy individuals
main factor driving the surge of TMAO levels, with the (95% confidence interval: 0.87, 3.07; P < 0.001). It has
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liver being the primary site of FMOs expression, alongside been demonstrated that plasma TMAO concentration
adrenals, lungs, and aorta which also express FMO3. increases within 72 h after the onset of atherosclerotic IS;
1
Eventually, TMA and TMAO are mostly excreted in the elevated plasma TMAO is independently associated with
urine through renal metabolism. atherosclerotic IS. Similar studies, including a meta-
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Plasma TMAO levels are influenced by various factors, analysis by Farhangi et al., found that when TMAO levels
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such as diet, gut microbiota, drug use, and FMO activity. are between 0 and 10 μmol/L, elevated TMAO levels are
In healthy individuals, the whole-body concentration of associated with an increased risk of IS. Moreover, the
TMAO varies dramatically after ingesting specific meals, association does not appear to be limited to the first stroke.
ranging from 0.5 to 5 μM. Li et al. demonstrated that The study found that elevated TMAO levels are linked to
2
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TMAO may serve as a new biomarker associated with an increased risk of IS recurrence in individuals who have
human health conditions. TMAO concentrations are previously undergone stroke. It was observed that TMAO
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linked to various health conditions, including all-cause was not only related to the incidence of a disease but also to
mortality, cardiovascular disease, hypertension, diabetes the prognosis. Dietary supplementation with choline and
mellitus, and chronic kidney disease. Similarly, in a recent TMAO has been found to both increase the size of cerebral
cohort study, the plasma concentrations of TMAO are infarction and cause more severe functional deficits after
considered to be a significant novel risk factor associated stroke injury. Exploring the relationship between TMAO
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with mortality in the elderly. At present, the consensus is and IS is not only helpful in reducing the incidence of a
4
that TMAO predominantly affects cholesterol metabolism, disease but also helpful in guiding treatment and predicting
exacerbates endothelial damage, raises platelet activity, the prognosis after IS. Therefore, it is necessary to study the
and triggers an inflammatory response when it comes to effect of TMAO on IS.

Volume 3 Issue 3 (2024) 2 doi: 10.36922/an.3005