脓毒症是引起儿童死亡的常见严重感染性疾病，部分患者即使有效控制感染，病死率仍居高不下。微生态失衡是脓毒症进展的关键，其快速检测和干预可为脓毒症精准诊疗提供新方法。课题组前期研究发现，脓毒症患儿肠道菌群紊乱，肠道苛养颗粒链菌（GE）的特异性增加不仅与疾病进展和不良预后相关，也与宿主T淋巴细胞m6A RNA甲基化修饰异常及免疫稳态失衡关联；GE培养上清可引起小鼠T淋巴细胞中RNA甲基催化酶METTL3表达上调及细胞功能异常。因此推测，肠道GE可能通过其代谢产物上调METTL3介导的m6A RNA甲基化修饰从而影响T淋巴细胞分化和功能，进而引起免疫失衡、加剧脓毒症进展。本项目拟在脓毒症患者、小鼠及相应的细胞模型中，利用多组学方法阐明GE及RNA甲基化修饰在脓毒症中的作用及机制，建立脓毒症肠道菌群失衡的快速检测和干预方法并探讨其临床应用，从而丰富对脓毒症发病机制的认识，并为其精准诊疗提供新方法。

Sepsis is a common serious infectious disease that causes death in children. Some patients still have a high mortality rate even if their infections have been effectively controlled. Micro-ecological imbalance is known to be the key to the progression of sepsis, and its rapid detection and intervention will provide a new effective approach to the precise diagnosis and treatment of sepsis. In our previous study, we have identified that the diversity of the intestinal flora in sepsis patients was decreased. More importantly, Granulicatella Elegans (GE) specifically enriched in the gut microbiota of sepsis patients, the abundance of which is not only related to disease progression and poor prognosis, but also to the abnormal m6A RNA modification of the host T lymphocytes and the imbalance of immune homeostasis. In addition, the culture supernatant of GE can cause up-regulation of mRNA methylation catalytic enzyme METTL3 and abnormal cell function in mouse T lymphocytes. Therefore, we hypothesize that intestinal GE may up-regulate METTL3-mediated m6A RNA methylation through its metabolites to affect T lymphocyte differentiation and function, thereby causing immune imbalance and aggravating the progression of sepsis. In the current project, we will use multi-omics methods to elucidate the role and mechanism of GE and m6A RNA methylation in the development and prognosis of sepsis in sepsis patients, mice and corresponding cell models. We will also establish rapid detection and intervention methods for intestinal flora imbalance in sepsis and explore its clinical application. The study will not only enrich the understanding of the pathogenesis of sepsis, but also provide new methods for its precise diagnosis and treatment.