Researchers have uncovered major changes in the gut bacteria of people with liver disease.
University of Birmingham-led research focused on the gut microbiome, and published in BMC Genome Medicine, provides clues about why chronic liver disease patients face an increased risk of serious infections.
Professor Lindsay Hall’s team from University of Birmingham collaborated with the Quadram Institute, Earlham Institute and Kings College London, to use advanced DNA sequencing technology to investigate the gut microbiome of patients with liver disease. Their findings reveal dramatic changes in gut bacteria as the disease becomes more severe, alongside increases in genes linked to antimicrobial resistance.
We found that some patients with the most severe liver disease had profoundly disrupted gut microbiomes, including the loss of many beneficial bacteria and the expansion of multi-drug-resistant species.
People living with advanced chronic liver disease (also known as liver cirrhosis) are particularly vulnerable to infections, which are a leading cause of hospitalisation and death in this patient group. They often require repeated courses of antibiotics, but scientists still do not fully understand the relationship between disease progression and the complex community of bacteria living in the gut.
The study analysed stool samples from 76 participants, including patients with stable cirrhosis, decompensated cirrhosis and acute-on-chronic liver failure, as well as healthy controls. Using long-read metagenomic sequencing, the team was able to identify both the bacteria present and the antimicrobial resistance genes they carried.
Among the most striking findings was the discovery that some of the sickest patients had severely disrupted gut microbiomes, almost entirely dominated by a single bacterial species, Enterococcus faecium. The presence of this clinically significant, multidrug-resistant pathogen is particularly relevant for patients because it can limit antibiotic treatment options and complicate infection management. These patients also had substantially lower microbial diversity, with many bacteria typically associated with a healthy gut greatly reduced or absent.
The study also revealed distinct antimicrobial resistance gene signatures associated with disease severity, providing a clearer picture of how both the microbiome and resistome change as liver disease progresses. These insights have the potential to help researchers better understand infection risk and develop new approaches to monitoring patient health.
Dr Hannah Trivett, lead author of the study from the University of Birmingham, said:
"People with advanced chronic liver disease are highly vulnerable to infections and treatment can be challenging because many of the bacteria involved are resistant to antibiotics. Using long-read sequencing, we found that some patients with the most severe liver disease had profoundly disrupted gut microbiomes, including the loss of many beneficial bacteria and the expansion of multi-drug-resistant species. These findings provide important new insights into the links between liver disease, the gut microbiome and antimicrobial resistance.”
Professor Lindsay Hall, senior and corresponding author on the study, said:
“These findings highlight the potential to use microbiome profiling to better understand why some patients with advanced chronic liver disease are more vulnerable to infection. Importantly, this knowledge could help guide future approaches that target the gut microbiome itself, supporting healthier microbial communities and reducing reliance on repeated courses of antibiotics.”
The researchers believe the findings highlight the potential of advanced sequencing technologies to improve understanding of host-microbiome interactions in advanced chronic liver disease and to support future research into infection risk, antimicrobial resistance and disease progression.
Chair of Microbiome Research
Staff Profile for Professor Lindsay Hall, Chair of Microbiome Research, Institute of Microbiology and Infection, University of Birmingham
Postdoctoral Reseach Fellow
Dr Hannah Trivett is a Research Fellow in the Department of Microbes, Infection and Microbiomes at the University of Birmingham, where she works within Prof Lindsay Hall's research group.
