Gut dysbiosis contributes to the development of Budd-Chiari syndrome through immune imbalance.

IF 5 2区 生物学 Q1 MICROBIOLOGY
mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-21 DOI:10.1128/msystems.00794-24
Qinwei Lu, Rongtao Zhu, Lin Zhou, Ruifang Zhang, Zhen Li, Peng Xu, Zhiwei Wang, Gang Wu, Jianzhuang Ren, Dechao Jiao, Yan Song, Jian Li, Weijie Wang, Ruopeng Liang, Xiuxian Ma, Yuling Sun
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引用次数: 0

Abstract

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.

Importance: 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.

肠道菌群失调会导致免疫失衡,从而引发巴德-恰里综合征。
布德-恰里综合征(B-CS)是一种以肝静脉流出道阻塞为特征的罕见致死性疾病。肠道微生物群与多种肝脏疾病有关,但其在 B-CS 发病机制中的意义尚不确定。首先,我们进行了一项病例对照研究(Ncase = 140,Ncontrol = 63),通过元基因组测序比较了 B-CS 和健康人的粪便微生物群。B-CS 患者的肠道微生物组成和活性发生了显著变化,元基因组构成不同,潜在致病菌(包括普雷沃特氏菌)增加,微生物功能与疾病相关。患者体内失衡的细胞因子被证明与肠道菌群失调有关,这让我们怀疑 B-CS 与肠道微生物群和免疫失调有关。接下来,对粪便微生物群移植(FMT)小鼠模型进行的 16S 核糖体 DNA 测序研究了肠道菌群失调与 B-CS 之间的联系。粪便微生物群移植模型显示肝组织受损、下腔静脉后移,并且在FMT小鼠紊乱的肠道微生物群中普雷沃茨菌增多。值得注意的是,B-CS-FMT 损伤了结肠组织的形态结构,增加了肠道通透性。此外,在 B-CS-FMT 小鼠中还观察到相同细胞因子(IL-5、IL-6、IL-9、IL-10、IL-17A、IL-17F 和 IL-13)和内毒素水平的显著增加。我们的研究表明,肠道微生物菌群失调可能会通过免疫失调导致 B-CS 的发生:本研究揭示了肠道微生物菌群失调可能导致布德-卡里综合征(B-CS)。肠道菌群失调增强了肠道通透性,有毒代谢产物和失衡的细胞因子激活了免疫系统。因此,致病因子的升级导致它们在门静脉中聚集,从而损害了肝实质和流出道。因此,我们认为肠道微生物菌群失调通过慢性全身性炎症诱发了免疫失衡,从而导致了 B-CS 的发生。此外,前驱菌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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
mSystems
mSystems Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
10.50
自引率
3.10%
发文量
308
审稿时长
13 weeks
期刊介绍: mSystems™ will publish preeminent work that stems from applying technologies for high-throughput analyses to achieve insights into the metabolic and regulatory systems at the scale of both the single cell and microbial communities. The scope of mSystems™ encompasses all important biological and biochemical findings drawn from analyses of large data sets, as well as new computational approaches for deriving these insights. mSystems™ will welcome submissions from researchers who focus on the microbiome, genomics, metagenomics, transcriptomics, metabolomics, proteomics, glycomics, bioinformatics, and computational microbiology. mSystems™ will provide streamlined decisions, while carrying on ASM''s tradition of rigorous peer review.
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