Systematic Insights into the Relationship between the Microbiota–Gut–Brain Axis and Stroke with the Focus on Tryptophan Metabolism

Stroke, as a serious cerebral vascular disease with high incidence and high rates of disability and mortality, has limited therapeutic options due to the narrow time window. Compelling evidence has highlighted the significance of the gut microbiota and gut-brain axis as critical regulatory factors affecting stroke. Along the microbiota-gut-brain axis, tryptophan metabolism further acquires increasing attention for its intimate association with central nervous system diseases. For the purpose of exploring the potential role of tryptophan metabolism in stroke and providing systematic insights into the intricate connection of the microbiota-gut-brain axis with the pathological procedure of stroke, this review first summarized the practical relationship between microbiota and stroke by compiling the latest case-control research. Then, the microbiota-gut-brain axis, as well as its interaction with stroke, were comprehensively elucidated on the basis of the basic anatomical structure and physiological function. Based on the crosstalk of microbiota-gut-brain, we further focused on the tryptophan metabolism from the three major metabolic pathways, namely, the kynurenine pathway, serotonin pathway, and microbial pathway, within the axis. Moreover, the effects of tryptophan metabolism on stroke were appreciated and elaborated here, which is scarcely found in other reviews. Hopefully, the systematic illustration of the mechanisms and pathways along the microbiota-gut-brain axis will inspire more translational research from metabolic perspectives, along with more attention paid to tryptophan metabolism as a promising pharmaceutical target in order to reduce the risk of stroke, mitigate the stroke progression, and ameliorate the stroke prognosis.