Recent studies have shown that stroke risk and outcomes are influenced by the microbiota composition and its strict relationship with the immune system. Age and sex are the main non-modifiable factors that shape microbiome composition. In order to evaluate the effects of these two variables on the microbiome in stroke pathogenesis we performed a systematic review of literature, including 10 studies in the final selection. In the critical analysis of data we focused on three aspects: gut permeability, molecular mediators (both inflammatory molecules and gut metabolites) and functional deficits. Males display higher post-stroke intestinal permeability than females and a youthful microbiome correlates with higher levels of mucin gene expression thus enhancing intestinal barrier function. Gut mast cells-derived histamine shows an age-dependent increase after stroke but it remains unknown whether it also shows sexual dimorphism in the context of stroke. IL-17 is significantly increased in males as compared to females. SCFAs promote recovery in aged mice. We registered a lack of evidence on the impact of hormonal differences on the stroke microbiome. An overall negative effect of aged microbiota on functional tests after stroke is a robust finding among many studies. However, the effects of sex-mediated microbiome variability on functional deficits after stroke remain elusive. The modifiable nature of the microbiome makes it suitable for therapeutic intervention, however we show that a lack of consideration for sex as a biological variable is a major limitation of current stroke clinical and pre-clinical microbiome research studies.
Keywords: Age; Gut permeability; Gut-brain axis; Microbiome; Microbiota; Sex; Stroke.
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