Influence of Intestinal Flora Metabolism on Aplastic Anemia and Its Mechanism

Aplastic anemia (AA) is an autoimmune disease mediated by T-lymphocyte hyperfunction and targeting the hematopoietic system. Recent studies have shown that gut flora metabolism has an important role in the human immune system, which in turn affects a number of immune system diseases. Our previous study found that flora metabolites and intestinal microbial species were significantly different in both AA patients and healthy individuals, with increased levels of isobutyric acid in plasma and bone marrow supernatants, and decreased levels of Citrobacter, among others, in the feces of AA patients. In this study, we conducted an animal model to further explore the mechanism. through mouse experiments, we found that the intestinal mucosa of AA model mice was thinner, less mucus, and fewer cup cells in comparison with healthy mice. transplantation of intestinal flora from normal mice in AA mice resulted in a significant improvement in the survival rate compared with that of the non-transplanted AA mice, and the analysis revealed that the proportion of CD4+ T cells in peripheral blood, spleen, and bone marrow was elevated in relation to absolute value and CD8+ T cells decreased in proportion and absolute value, and pathologic analysis showed improved myeloproliferation. In addition, isobutyric acid, in normal mice, resulted in an increase in the proportion of CD8+ T cells, a trend identical to that of AA, with a tendency to exacerbate the condition in AA mice. This suggests that intestinal flora may affect immune cells by influencing the intestinal mucosal barrier and thus AA disease progression.再生障碍性贫血(AA)是一种由t淋巴细胞功能亢进介导的以造血系统为靶点的自身免疫性疾病。最近的研究表明，肠道菌群代谢在人体免疫系统中具有重要作用，进而影响许多免疫系统疾病。我们前期研究发现AA患者与健康个体的菌群代谢物和肠道微生物种类存在显著差异，AA患者血浆和骨髓上清液中异丁酸水平升高，粪便中柠檬酸杆菌(Citrobacter)水平降低。在本研究中，我们通过动物模型来进一步探讨其机制。通过小鼠实验，我们发现AA模型小鼠的肠黏膜较健康小鼠更薄，粘液更少，杯状细胞更少。正常小鼠肠道菌群移植AA小鼠的存活率较未移植AA小鼠明显提高，外周血、脾、骨髓中CD4 T细胞比例绝对值升高，CD8 T细胞比例绝对值降低，病理分析显示骨髓增生改善。此外，异丁酸在正常小鼠中导致CD8 T细胞比例增加，与AA相同，并有加重AA小鼠病情的趋势。这表明肠道菌群可能通过影响肠黏膜屏障从而影响免疫细胞，从而影响AA疾病的进展。

No relevant conflicts of interest to declare.