Bone marrow mesenchymal stem cell therapy regulates gut microbiota to improve post-stroke neurological function recovery in rats

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.

Core Tip: Bone marrow mesenchymal stem cell (BMSC) transplantation provides a novel approach for ischemic stroke therapy. Studies on the “gut-brain axis” indicate that gut microbiota dysbiosis affects stroke prognosis. We investigated the interactions between BMSCs and gut microbiota. Our findings indicate that the therapeutic mechanism of BMSCs on ischemic stroke treatment may involve the regulation of microbiome structure and function.

• Citation: Zhao LN, Ma SW, Xiao J, Yang LJ, Xu SX, Zhao L. Bone marrow mesenchymal stem cell therapy regulates gut microbiota to improve post-stroke neurological function recovery in rats. World J Stem Cells 2021; 13(12): 1905-1917
• URL: https://www.wjgnet.com/1948-0210/full/v13/i12/1905.htm
• DOI: https://dx.doi.org/10.4252/wjsc.v13.i12.1905