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肠道微生物群失调与终末期肝病患者门静脉血栓形成无关:一项横断面研究。

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

作者信息

Aleksandrova Rali R, Nieuwenhuis Lianne M, Karmi Naomi, Zhang Shuyan, Swarte Johann Casper, Björk Johannes R, Gacesa Ranko, Blokzijl Hans, Connelly Margery A, Weersma Rinse K, Lisman Ton, Festen Eleonora A M, de Meijer Vincent E

机构信息

Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

出版信息

J Thromb Haemost. 2025 Apr;23(4):1407-1415. doi: 10.1016/j.jtha.2024.12.036. Epub 2025 Jan 9.

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.

摘要

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。ESLD患者的门静脉被认为是一个炎症性血管床,这是由于内毒素和细胞因子从肠道易位所致。我们假设促炎性肠道微生物群和血栓形成的驱动因素三甲胺N-氧化物(TMAO)水平升高可能导致PVT的发生。

目的

我们研究了肠道微生物群多样性、细菌种类、代谢途径和TMAO水平是否与ESLD患者的PVT相关。

方法

通过移植线生物样本库和队列研究收集ESLD患者及健康对照者的粪便样本、血浆样本和数据。PVT定义为在粪便样本采集前或后一年内门静脉内的血栓。粪便样本采用鸟枪法宏基因组测序进行分析,血浆中的TMAO水平使用Vantera临床分析仪进行测量。

结果

纳入了102例ESLD患者,其中23例患有PVT,以及246例健康对照者。PVT患者和非PVT患者之间的肠道微生物群多样性没有显著差异(P = 0.18)。两个ESLD组的α多样性均显著低于对照组。与非PVT患者相比,PVT患者的脆弱拟杆菌和3种梭菌属物种增加。三组之间的TMAO水平没有显著差异。

结论

我们观察到ESLD患者与对照组之间肠道微生物群存在显著差异,但ESLD伴或不伴PVT患者之间差异极小。在我们的队列中,肠道源性促炎状态与ESLD患者PVT的存在无关。

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