Stroke and Vascular Cognitive Impairment: The Role of Intestinal Microbiota Metabolite TMAO

The gut microbiome interacts with the brain bidirectionally through the microbiome-gut-brain axis, which plays a key role in regulating various nervous system pathophysiological processes. Trimethylamine N-oxide (TMAO) is produced by choline metabolism through intestinal microorganisms, which can cross the blood-brain barrier to act on the central nervous system. Previous studies have shown that elevated plasma TMAO concentrations increase the risk of major adverse cardiovascular events, but there are few studies on TMAO in cerebrovascular disease and vascular cognitive impairment. This review summarized a decade of research on the impact of TMAO on stroke and related cognitive impairment, with particular attention to the effects on vascular cognitive disorders. We demonstrated that TMAO has a marked impact on the occurrence, development, and prognosis of stroke by regulating cholesterol metabolism, foam cell formation, platelet hyperresponsiveness and thrombosis, and promoting inflammation and oxidative stress. TMAO can also influence the cognitive impairment caused by Alzheimer's disease and Parkinson's disease via inducing abnormal aggregation of key proteins, affecting inflammation and thrombosis. However, although clinical studies have confirmed the association between the microbiome-gut-brain axis and vascular cognitive impairment (cerebral small vessel disease and post-stroke cognitive impairment), the molecular mechanism of TMAO has not been clarified, and TMAO precursors seem to play the opposite role in the process of post-stroke cognitive impairment. In addition, several studies have also reported the possible neuroprotective effects of TMAO. Existing therapies for these diseases targeted to regulate intestinal flora and its metabolites have shown good efficacy. TMAO is probably a new target for early prediction and treatment of stroke and vascular cognitive impairment.