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

Collaborators, Affiliations

Collaborators

TransplantLines Investigators:
Coby Annema⁸, Stephan J L Bakker⁹, Stefan P Berger⁹, Hans Blokzijl¹⁰, Frank A J A Bodewes¹¹, Marieke T de Boer¹², Kevin Damman¹³, Martin H de Borst⁹, Arjan Diepstra¹⁴, Gerard Dijkstra¹⁰, Caecilia S E Doorenbos⁹, Rianne M Douwes⁹, Michele F Eisenga⁹, Michiel E Erasmus¹⁵, C Tji Gan¹⁶, Antonio W Gomes Neto⁹, Eelko Hak¹⁷, Jip Jonker⁹, Frank Klont¹⁸, Tim J Knobbe⁹, Daan Kremer⁹, Henri G D Leuvenink¹⁹, Willem S Lexmond¹¹, Vincent E de Meijer¹², Hubert G M Niesters²⁰, Gertrude J Nieuwenhuijs-Moeke²¹, L Joost van Pelt¹⁹, Robert A Pol²², Anna M Posthumus⁹, Adelita V Ranchor²³, Jan Stephan F Sanders⁹, Marion J Siebelink²⁴, Riemer J H J A Slart²⁵, J Casper Swarte⁹, Daan J Touw²⁶, Marius C van den Heuvel¹⁴, Coretta van Leer-Buter²⁷, Marco van Londen⁹, Charlotte A Te Velde Keyzer⁹, Erik A M Verschuuren¹⁶, Michel J Vos²⁸, Rinse K Weersma¹⁰

Affiliations

¹ 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.
² Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³ Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁴ Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁵ Laboratory Corporation of America Holdings (LabCorp), Morrisville, North Carolina, USA.
⁶ Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Surgery, University of Groningen, Surgical Research Laboratory, University Medical Center Groningen, Groningen, the Netherlands.
⁷ Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: v.e.de.meijer@umcg.nl.
⁸ Department of Health Sciences, Section of Nursing Science, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
⁹ Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
¹⁰ Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
¹¹ Department of Pediatrics, division of Pediatric Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
¹² Department of Surgery, division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
¹³ Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
¹⁴ Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB Groningen, The Netherlands.
¹⁵ Department of Cardiac Surgery, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
¹⁶ Department of Respiratory Diseases, Tuberculosis and Lung Transplantation, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
¹⁷ Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
¹⁸ Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University of Groningen, 9700 RB Groningen, The Netherlands; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
¹⁹ Department of Surgery, Surgical Research Laboratory, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
²⁰ Department of Medical Microbiology and Infection Prevention, Division of Clinical Virology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
²¹ Department of Anesthesiology, University of Groningen, University Medical Centre Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
²² Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
²³ Department of Health Psychology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
²⁴ University Medical Center Groningen Transplant Center, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
²⁵ Medical Imaging Centre, Department of Nuclear Medicine and Molecular Imaging (EB50), University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
²⁶ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; Department of Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
²⁷ Department of Virology, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands.
²⁸ Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands.

PMID: 39798925
DOI: 10.1016/j.jtha.2024.12.036

Free article

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

Rali R Aleksandrova et al. J Thromb Haemost. 2025 Apr.

Free article

. 2025 Apr;23(4):1407-1415.

doi: 10.1016/j.jtha.2024.12.036. Epub 2025 Jan 9.

Collaborators

TransplantLines Investigators:
Coby Annema⁸, Stephan J L Bakker⁹, Stefan P Berger⁹, Hans Blokzijl¹⁰, Frank A J A Bodewes¹¹, Marieke T de Boer¹², Kevin Damman¹³, Martin H de Borst⁹, Arjan Diepstra¹⁴, Gerard Dijkstra¹⁰, Caecilia S E Doorenbos⁹, Rianne M Douwes⁹, Michele F Eisenga⁹, Michiel E Erasmus¹⁵, C Tji Gan¹⁶, Antonio W Gomes Neto⁹, Eelko Hak¹⁷, Jip Jonker⁹, Frank Klont¹⁸, Tim J Knobbe⁹, Daan Kremer⁹, Henri G D Leuvenink¹⁹, Willem S Lexmond¹¹, Vincent E de Meijer¹², Hubert G M Niesters²⁰, Gertrude J Nieuwenhuijs-Moeke²¹, L Joost van Pelt¹⁹, Robert A Pol²², Anna M Posthumus⁹, Adelita V Ranchor²³, Jan Stephan F Sanders⁹, Marion J Siebelink²⁴, Riemer J H J A Slart²⁵, J Casper Swarte⁹, Daan J Touw²⁶, Marius C van den Heuvel¹⁴, Coretta van Leer-Buter²⁷, Marco van Londen⁹, Charlotte A Te Velde Keyzer⁹, Erik A M Verschuuren¹⁶, Michel J Vos²⁸, Rinse K Weersma¹⁰

Affiliations

¹ 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.
² Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³ Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁴ Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁵ Laboratory Corporation of America Holdings (LabCorp), Morrisville, North Carolina, USA.
⁶ Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Surgery, University of Groningen, Surgical Research Laboratory, University Medical Center Groningen, Groningen, the Netherlands.
⁷ Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: v.e.de.meijer@umcg.nl.
⁸ Department of Health Sciences, Section of Nursing Science, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
⁹ Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
¹⁰ Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
¹¹ Department of Pediatrics, division of Pediatric Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
¹² Department of Surgery, division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
¹³ Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
¹⁴ Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB Groningen, The Netherlands.
¹⁵ Department of Cardiac Surgery, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
¹⁶ Department of Respiratory Diseases, Tuberculosis and Lung Transplantation, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
¹⁷ Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
¹⁸ Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University of Groningen, 9700 RB Groningen, The Netherlands; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
¹⁹ Department of Surgery, Surgical Research Laboratory, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
²⁰ Department of Medical Microbiology and Infection Prevention, Division of Clinical Virology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
²¹ Department of Anesthesiology, University of Groningen, University Medical Centre Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
²² Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
²³ Department of Health Psychology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
²⁴ University Medical Center Groningen Transplant Center, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
²⁵ Medical Imaging Centre, Department of Nuclear Medicine and Molecular Imaging (EB50), University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
²⁶ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; Department of Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
²⁷ Department of Virology, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands.
²⁸ Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands.

PMID: 39798925
DOI: 10.1016/j.jtha.2024.12.036

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.

Keywords: dysbiosis; gastrointestinal microbiome; inflammation; liver cirrhosis; portal vein thrombosis.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interests M.A.C. is an employee of LabCorp. M.A.C. assisted with the generation of the TMAO measurements. Labcorp was not involved in the study design, the data analysis, or the decision to publish the results. The rest of the authors declared they have no competing interests.

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

LinkOut - more resources

Full Text Sources
- Elsevier Science
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical