Dong Xiaotian, Feng Xudong, Liu Jingqi, Xu Yanping, Pan Qiaoling, Ling Zongxin, Yu Jiong, Yang Jinfeng, Li Lanjuan, Cao Hongcui
State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Rd., Hangzhou City 310003, China.
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Rd., Hangzhou City 310003, China.
Stem Cells Int. 2019 Feb 5;2019:2403793. doi: 10.1155/2019/2403793. eCollection 2019.
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.
In this study, compact bone-derived MSCs were injected into mice after carbon tetrachloride (CCl) 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.
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 CCl-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 and and increased abundance of Firmicutes , , and at the initial time point compared with that in CCl-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.
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.
间充质干细胞（MSC）移植对急性肝损伤的保护机制在肝脏内已得到充分研究。然而，在此过程中肠道微生物群的相关变化却知之甚少。
在本研究中，在给予小鼠四氯化碳（CCl）后，将致密骨源性MSC注射到小鼠体内。通过生存率、生化和病理结果评估MSC的潜在治疗效果。通过对盲肠和结肠内容物的16S rRNA扩增子文库进行测序，评估微生物群落的整体结构变化和肠道微生物群的改变。
MSC显著降低了天冬氨酸转氨酶和丙氨酸转氨酶的血清水平，改善了组织病理学和生存率。与MSC移植小鼠相比，在48小时时，CCl处理的小鼠中紧密连接蛋白表达降低且染色不连续，以及紧密连接被破坏。此外，与CCl处理的小鼠相比，将MSC移植到肝脏导致肠道微生物群发生变化，在初始时间点表现为拟杆菌门丰度降低，厚壁菌门、、和丰度增加。此外，基于Greengenes数据库通过未观察状态的重建（PICRUSt）对群落进行系统发育研究，揭示了MSC移植小鼠的功能生物标志物，这些标志物涉及细胞运动、信号转导、膜转运、转录以及脂质、辅因子、维生素、萜类化合物、聚酮化合物以及外源性物质的代谢。
由于向肝脏输注MSC导致的厚壁菌门/拟杆菌门比例的初始变化，维持了肠道黏膜生物学和内环境稳态，这可能有利于肝脏修复。
