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

BACKGROUND: Portal vein thrombosis (PVT) is a common complication in patients with end-stage liver disease (ESLD). The portal vein in ESLD patients is proposedly an inflammatory vascular bed due to translocation of endotoxins and cytokines from the gut. We hypothesized that a pro-inflammatory 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 ESLD patients.

METHODS: Fecal samples, plasma samples and data from ESLD patients 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: 102 ESLD patients, 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=0.18). Both ESLD groups had significantly lower alpha-diversity compared with controls. Bacteroides fragilis and three Clostridiales species were increased in patients with PVT compared to without PVT. TMAO levels between the three groups were not significantly different.

CONCLUSION: We observed profound differences in gut microbiota between ESLD patients and controls, but minimal differences between ESLD patients with or without PVT. In our cohort, a gut-derived pro-inflammatory state was not associated with presence of PVT in ESLD patients.