Budd-Chiari综合征(B-CS)是一种罕见且致命的疾病,其特征是肝静脉流出道阻塞。肠道菌群与许多肝脏疾病有关,但其在B-CS发病机制中的意义尚不明确。首先,我们进行了一项病例对照研究(Ncase=140,Ncontrol=63),通过宏基因组学测序比较了B-CS和健康个体的粪便微生物群.B-CS患者肠道微生物组成和活性发生显著变化,具有不同的宏基因组组成,增加潜在的致病细菌,包括普雷沃氏菌,和疾病相关的微生物功能。患者的细胞因子失衡被证明与肠道菌群失调有关,这使我们怀疑B-CS与肠道微生物群和免疫失调有关。接下来,粪便微生物移植(FMT)小鼠模型上的16S核糖体DNA测序检查了肠道菌群失调与B-CS之间的联系。FMT模型显示肝脏组织受损,下腔静脉后,在FMT小鼠的肠道微生物群中增加了Prevotella。值得注意的是,B-CS-FMT损害结肠组织的形态结构并增加肠通透性。此外,显著增加相同的细胞因子(IL-5,IL-6,IL-9,IL-10,IL-17A,IL-17F,观察B-CS-FMT小鼠的IL-13)和内毒素水平。我们的研究表明,肠道微生物菌群失调可能通过免疫失调引起B-CS。
目的:本研究揭示肠道微生物菌群失调可能导致布加综合征(B-CS)。肠道菌群失调增强肠道通透性,毒性代谢物和不平衡的细胞因子激活了免疫系统。因此,致病因素的升级导致它们集中在门静脉,从而损害肝实质和流出道。因此,我们提出肠道微生物菌群失调是由慢性全身性炎症引起的免疫失衡,为B-CS的发展做出了贡献。此外,Prevotella可能介导炎症发展和免疫失衡,在B-CS发病机制中显示出潜力。
Budd-Chiari syndrome (B-CS) is a rare and lethal condition characterized by hepatic venous outflow tract blockage. Gut microbiota has been linked to numerous hepatic disorders, but its significance in B-CS pathogenesis is uncertain. First, we performed a case-control study (Ncase = 140, Ncontrol = 63) to compare the fecal microbiota of B-CS and healthy individuals by metagenomics sequencing. B-CS patients\' gut microbial composition and activity changed significantly, with a different metagenomic makeup, increased potentially pathogenic bacteria, including Prevotella, and disease-linked microbial function. Imbalanced cytokines in patients were demonstrated to be associated with gut dysbiosis, which led us to suspect that B-CS is associated with gut microbiota and immune dysregulation. Next, 16S ribosomal DNA sequencing on fecal microbiota transplantation (FMT) mice models examined the link between gut dysbiosis and B-CS. FMT models showed damaged liver tissues, posterior inferior vena cava, and increased Prevotella in the disturbed gut microbiota of FMT mice. Notably, B-CS-FMT impaired the morphological structure of colonic tissues and increased intestinal permeability. Furthermore, a significant increase of the same cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, IL-17F, and IL-13) and endotoxin levels in B-CS-FMT mice were observed. Our study suggested that gut microbial dysbiosis may cause B-CS through immunological dysregulation.
OBJECTIVE: This study revealed that gut microbial dysbiosis may cause Budd-Chiari syndrome (B-CS). Gut dysbiosis enhanced intestinal permeability, and toxic metabolites and imbalanced cytokines activated the immune system. Consequently, the escalation of causative factors led to their concentration in the portal vein, thereby compromising both the liver parenchyma and outflow tract. Therefore, we proposed that gut microbial dysbiosis induced immune imbalance by chronic systemic inflammation, which contributed to the B-CS development. Furthermore, Prevotella may mediate inflammation development and immune imbalance, showing potential in B-CS pathogenesis.