Abstract
Background The mechanisms of mesenchymal stem cell (MSC) transplantation to protect against acute liver injury have been well studied within the liver. However, the associated changes in the intestinal microbiota during this process are poorly understood. Methods In this study, compact bone-derived MSCs were injected into mice after carbon tetrachloride (CCl4) administration. Potential curative effect of MSC was evaluated by survival rate and biochemical and pathological results. Overall structural changes of microbial communities and alterations in the intestinal microbiota were assessed by sequenced 16S rRNA amplicon libraries from the contents of the cecum and colon. Results MSCs significantly reduced the serum levels of aspartate transaminase and alanine transaminase and improved the histopathology and survival rate. Lower expression and discontinuous staining of zonula occludens, as well as disrupted tight junctions, were observed in CCl4-treated mice at 48 h compared with MSC-transplanted mice. Moreover, MSC transplantation to the liver leads to intestinal microbiota changes that were reflected in the decreased abundance of Bacteroidetes S24-7 and Bacteroidaceae and increased abundance of Firmicutes Clostridiales, Ruminococcaceae, and Lactobacillus at the initial time point compared with that in CCl4-treated mice. In addition, phylogenetic investigation of communities by the reconstruction of unobserved states (PICRUSt) based on the Greengenes database revealed functional biomarkers of MSC-transplanted mice involved in cell motility, signal transduction, membrane transport, transcription, and metabolism of lipids, cofactors, vitamins, terpenoids, and polyketides, as well as xenobiotics. Conclusion The initial alterations in the Firmicutes/Bacteroidetes ratio, which resulted from MSC infusion to the liver, maintain intestinal mucosal biology and homeostasis that may be beneficial to liver repair.
Highlights
The transplantation of mesenchymal stem cells (MSCs) demonstrates protective effects in various models of organ injury [1, 2], including carbon tetrachloride- (CCl4-) induced acute liver injury [3], implying that MSCs can be therapeutically effective [4,5,6]
Because acute liver injury impairs the intestinal mucosa structure and tight junctions (TJs) [11, 12], resulting in bacterial translocation and portal endotoxemia that can serve as a contributory mechanism of hepatotoxicity [13,14,15], we considered that the therapeutic effect of MSCs might involve microbiota changes that promote barrier integrity
All the sequences were clustered into 1517 operational taxonomic units (OTUs) using QIIME based on 97% sequence similarity and classified into 249 bacterial groups at the genus level
Summary
The transplantation of mesenchymal stem cells (MSCs) demonstrates protective effects in various models of organ injury [1, 2], including carbon tetrachloride- (CCl4-) induced acute liver injury [3], implying that MSCs can be therapeutically effective [4,5,6]. Because acute liver injury impairs the intestinal mucosa structure and tight junctions (TJs) [11, 12], resulting in bacterial translocation and portal endotoxemia that can serve as a contributory mechanism of hepatotoxicity [13,14,15], we considered that the therapeutic effect of MSCs might involve microbiota changes that promote barrier integrity. For. The mechanisms of mesenchymal stem cell (MSC) transplantation to protect against acute liver injury have been well studied within the liver. MSC transplantation to the liver leads to intestinal microbiota changes that were reflected in the decreased abundance of Bacteroidetes S24-7 and Bacteroidaceae and increased abundance of Firmicutes Clostridiales, Ruminococcaceae, and Lactobacillus at the initial time point compared with that in CCl4-treated mice. The initial alterations in the Firmicutes/Bacteroidetes ratio, which resulted from MSC infusion to the liver, maintain intestinal mucosal biology and homeostasis that may be beneficial to liver repair
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