Crossroad Between Gut Microbiome and Ischemic Stroke: Underlying Pathways and Therapeutic Possibilities

Stroke is a cerebrovascular condition that has emerged as the major cause of death globally, among other non-communicable diseases, due to its pathophysiological complexity and varied etiologies. Ischemic stroke (IS) represents the most prevalent subtype accounting for more than 70% of all stroke cases worldwide. The gut microbiome is considered the most abundant pool of microorganisms, which release metabolic products that facilitate gut-brain signaling. Despite advancements, the precise processes by which gut microbes influence stroke pathogenesis are not entirely understood. This review explores the immunomodulatory impact of gut-derived metabolites in IS, with a focus on short-chain fatty acids (SCFAs) and other bioactive substances. A comprehensive literature search was undertaken using MeSH terms such as gut microbiome, ischemic stroke, cerebral ischemia, brain infarction, intestinal flora, and gut-brain axis. We address how metabolites such as short-chain fatty acids produced by gut bacteria influence the host's immune system, which in turn affects the activity of neural networks linked to atherosclerosis, a major underlying mechanism of IS. Furthermore, this review also looks at new research opportunities and highlights evidence from studies conducted on humans and animals.