BACKGROUND As a cellular mode of therapy, bone marrow mesenchymal stem cells (BMSCs) are used to treat stroke. However, their mechanisms in stroke treatment have not been established. Recent evidence suggests that regulation of dysregulated gut flora after stroke affects stroke outcomes. AIM To investigate the effects of BMSCs on gut microbiota after ischemic stroke. METHODS A total of 30 Sprague-Dawley rats were randomly divided into three groups, including sham operation control group, transient middle cerebral artery occlusion (MCAO) group, and MCAO with BMSC treatment group. The modified Neurological Severity Score (mNSS), beam walking test, and Morris water maze test were used to evaluate neurological function recovery after BMSC transplantation. Nissl staining was performed to elucidate on the pathology of nerve cells in the hippocampus. Feces from each group of rats were collected and analyzed by 16s rDNA sequencing. RESULTS BMSC transplantation significantly reduced mNSS ( P < 0.01). Rats performed better in the beam walking test in the BMSC group than in the MCAO group ( P < 0.01). The Morris water maze test revealed that the BMSC treatment group exhibited a significant improvement in learning and memory. Nissl staining for neuronal damage assessment after stroke showed that in the BMSC group, cells were orderly arranged with significantly reduced necrosis. Moreover, BMSCs regulated microbial structure composition . In rats treated with BMSCs, the abundance of potential short-chain fatty acid producing bacteria and Lactobacillus was increased. CONCLUSION BMSC transplantation is a potential therapeutic option for ischemic stroke, and it promotes neurological functions by regulating gut microbiota dysbiosis.

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Background Stroke is not only a major cause of disability but also the third leading cause of death, following heart disease and cancer. It has been established that stroke causes permanent disability in 80% of survivors. However, current treatment options for this patient population are limited. Inflammation and immune response are major features that are well‐recognized to occur after a stroke. The gastrointestinal tract hosts complex microbial communities, the largest pool of immune cells, and forms a bidirectional regulation brain‐gut axis with the brain. Recent experimental and clinical studies have highlighted the importance of the relationship between the intestinal microenvironment and stroke. Over the years, the influence of the intestine on stroke has emerged as an important and dynamic research direction in biology and medicine. Aims In this review, we describe the structure and function of the intestinal microenvironment and highlight its cross‐talk relationship with stroke. In addition, we discuss potential strategies aiming to target the intestinal microenvironment during stroke treatment. Conclusion The structure and function of the intestinal environment can influence neurological function and cerebral ischemic outcome. Improving the intestinal microenvironment by targeting the gut microbiota may be a new direction in treating stroke.