Role of the gut microbiota in complications after ischemic stroke

Abstract

Ischemic stroke (IS) is a serious central nervous system disease. Post-IS complications, such as post-stroke cognitive impairment (PSCI), post-stroke depression (PSD), hemorrhagic transformation (HT), gastrointestinal dysfunction, cardiovascular events, and post-stroke infection (PSI), result in neurological deficits. The microbiota-gut-brain axis (MGBA) facilitates bidirectional signal transduction and communication between the intestines and the brain. Recent studies have reported alterations in gut microbiota diversity post-IS, suggesting the involvement of gut microbiota in post-IS complications through various mechanisms such as bacterial translocation, immune regulation, and production of gut bacterial metabolites, thereby affecting disease prognosis. In this review, to provide insights into the prevention and treatment of post-IS complications and improvement of the long-term prognosis of IS, we summarize the interaction between the gut microbiota and IS, along with the effects of the gut microbiota on post-IS complications.

Keywords: complication; gut microbiota; ischemic stroke; prognosis; treatment.

Figure 1

Complications after ischemic stroke (IS). Post-IS complications involve the central nervous, respiratory, circulatory, digestive, and urinary systems and can include post-stroke cognitive impairment (PSCI), post-stroke depression (PSD), hemorrhagic transformation (HT), gastrointestinal dysfunction, cardiovascular events, and post-stroke infection (PSI). Figure generated by BioRender.com.

Figure 2

Gut microbiota and post-stroke gastrointestinal dysfunction pathogenesis. Increased abundance of gut microbiota, decreased beneficial metabolites short-chain fatty acids (SCFAs), and increased LPS of Gram-negative bacteria post IS, triggered an inflammatory response with increased expression levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, and cytokine interferon-γ (IFN-γ). The cytotoxic effects of inflammatory substances lead to intestinal microvillus damage and reduced expression of intestinal epithelial tight junction proteins, triggering intestinal epithelial barrier dysfunction and intestinal leakage, which can lead to intestinal motility disorders, intestinal paralysis, and other gastrointestinal complications. Impairment of intestinal barrier function allows inflammatory cytokines, bacteria, and toxic intestinal metabolites to cross the damaged intestinal epithelial barrier and enter the circulatory system, exacerbating gastrointestinal dysfunction and even triggering enterogenic sepsis. Figure generated by BioRender.com.