Title:Stroke and Vascular Cognitive Impairment: The Role of Intestinal
Microbiota Metabolite TMAO
Volume: 23
Issue: 1
Author(s): Ruxin Tu and Jian Xia*
Affiliation:
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
- Human Clinical Research Center for Cerebrovascular Disease, Changsha, China
Keywords:
Gut microbiome, TMAO, stroke, vascular cognitive impairment, post-stroke cognitive impairment, dementia.
Abstract: The gut microbiome interacts with the brain bidirectionally through the microbiome-gutbrain
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 poststroke
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.