RT Journal Article
SR Electronic
T1 Bone marrow-derived mesenchymal stem cell ameliorates post-stroke enterobacterial translocation through liver-gut axis
JF Stroke and Vascular Neurology
JO Stroke Vasc Neurol
FD BMJ Publishing Group Ltd
SP svn-2024-003494
DO 10.1136/svn-2024-003494
A1 Su, Xiaotao
A1 Li, Tiemei
A1 Wang, Yuge
A1 Wei, Lei
A1 Jian, Banghao
A1 Kang, Xinmei
A1 Hu, Mengyan
A1 Li, Chunyi
A1 Wang, Shisi
A1 Lu, Danli
A1 Shen, Shishi
A1 Huang, Huipeng
A1 Liu, Yuxin
A1 Deng, Xiaohui
A1 Zhang, Bingjun
A1 Cai, Wei
A1 Lu, Zhengqi
YR 2024
UL http://svn.bmj.com/content/early/2024/10/04/svn-2024-003494.abstract
AB Background Enterobacterial translocation is a leading contributor to fatal infection among patients with acute ischaemic stroke (AIS). Accumulative evidence suggests that mesenchymal stem cell (MSC) effectively ameliorates stroke outcomes. Whether MSC could inhibit post-stroke enterobacterial translocation remains elusive.Methods Patients with AIS and healthy individuals were enrolled in the study. Mice subjected to transient middle cerebral artery occlusion were treated with bone marrow-derived MSC (BM-MSC) right after reperfusion. Enterobacterial translocation was evaluated with Stroke Dysbiosis Index and circulating endotoxin. Thickness of mucus was assessed with Alcian blue staining. Hepatic glucocorticoid (GC) metabolism was analysed with expression of HSD11B2, HSD11B1 and SRD5A1.Results We report that the gut mucus layer was attenuated after the stroke leading to pronounced enterobacterial translocation. The attenuation of the gut mucus was attributed to diminished mucin production by goblet cells in response to the elevated systemic GC after cerebral ischaemia. Transferred-BM-MSC restored the mucus thickness, thus preserving gut microbiota homeostasis and preventing enterobacterial invasion. Mechanistically, the transferred-BM-MSC stationed in the liver and enhanced peroxisome proliferator-activated receptor γ signalling in hepatocytes. Consequently, expression of HSD11B2 and SRD5A1 was increased while HSD11B1 expression was downregulated which promoted GC catabolism and subsequently restored mucin production.Conclusions Our findings reveal that MSC transfer improves post-stroke gut barrier integrity and inhibits enterobacterial translocation by enhancing the hepatic GC metabolism thus representing a protective modulator of the liver-gut-brain axis in AIS.Data are available upon reasonable request. All data are available in the main text or the supplementary materials. Additional data related to this paper may be requested from the authors.