Gut microbiome dysbiosis is not associated with portal vein thrombosis in patients with end-stage liver disease: a cross-sectional study

IF 5.5 2区 医学 Q1 HEMATOLOGY
Rali R. Aleksandrova , Lianne M. Nieuwenhuis , Naomi Karmi , Shuyan Zhang , Johann Casper Swarte , Johannes R. Björk , Ranko Gacesa , Hans Blokzijl , Margery A. Connelly , Rinse K. Weersma , Ton Lisman , Eleonora A.M. Festen , Vincent E. de Meijer
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Abstract

Background

Portal vein thrombosis (PVT) is a common complication in patients with end-stage liver disease (ESLD). The portal vein in patients with ESLD is proposedly an inflammatory vascular bed due to translocation of endotoxins and cytokines from the gut. We hypothesized that a proinflammatory gut microbiome and elevated trimethylamine N-oxide (TMAO), a driver of thrombosis, may contribute to PVT development.

Objectives

We investigated whether gut microbiome diversity, bacterial species, metabolic pathways, and TMAO levels are associated with PVT in patients with ESLD.

Methods

Fecal samples, plasma samples, and data from patients with ESLD and healthy controls were collected through the TransplantLines Biobank and Cohort Study. PVT was defined as a thrombus in the portal vein within a year prior to or after fecal sample collection. Fecal samples were analyzed using Shotgun Metagenomic Sequencing, and TMAO levels were measured in plasma using a Vantera Clinical Analyzer.

Results

One hundred two patients with ESLD, of which 23 with PVT, and 246 healthy controls were included. No significant difference in gut microbiome diversity was found between patients with PVT and without PVT (P = .18). Both ESLD groups had significantly lower alpha diversity than controls. Bacteroides fragilis and 3 Clostridiales species were increased in patients with PVT compared with without PVT. TMAO levels between the 3 groups were not significantly different.

Conclusion

We observed profound differences in gut microbiota between patients with ESLD and controls, but minimal differences between patients with ESLD with or without PVT. In our cohort, a gut-derived proinflammatory state was not associated with presence of PVT in patients with ESLD.
终末期肝病患者肠道微生物群失调与门静脉血栓形成无关:一项横断面研究
背景:门静脉血栓形成(PVT)是终末期肝病(ESLD)患者的常见并发症。由于肠道内毒素和细胞因子的易位,ESLD患者的门静脉被认为是炎症血管床。我们假设促炎肠道微生物群和三甲胺n -氧化物(TMAO)升高(血栓形成的驱动因素)可能有助于PVT的发展。目的:我们研究ESLD患者肠道微生物群多样性、细菌种类、代谢途径和TMAO水平是否与PVT相关。方法:通过TransplantLines生物库和队列研究收集ESLD患者和健康对照者的粪便、血浆和数据。PVT被定义为在收集粪便样本之前或之后一年内门静脉内的血栓。使用Shotgun宏基因组测序分析粪便样本,使用Vantera®临床分析仪测量血浆中TMAO水平。结果:纳入ESLD患者102例,其中伴PVT患者23例,健康对照246例。PVT患者与非PVT患者肠道菌群多样性差异无统计学意义(P=0.18)。与对照组相比,两个ESLD组的α多样性显著降低。PVT患者的脆弱拟杆菌和3种梭菌均较无PVT患者增加,三组间TMAO水平无显著差异。结论:我们观察到ESLD患者和对照组之间的肠道微生物群存在显著差异,但伴有或不伴有PVT的ESLD患者之间的差异很小。在我们的队列中,肠道源性促炎状态与ESLD患者中PVT的存在无关。
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来源期刊
Journal of Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis 医学-外周血管病
CiteScore
24.30
自引率
3.80%
发文量
321
审稿时长
1 months
期刊介绍: The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.
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