by King's College London

Microbial diversity and community structure alterations by cirrhosis severity. Credit: Journal of Hepatology (2024). DOI: 10.1016/j.jhep.2024.09.046

The bacterial changes also correlate with increased antibiotic resistance, highlighting the need for better targeting of antibiotic treatment.

This is the first study to comprehensively describe the degree of overlap between the bacteria in the mouth and gut, and the factors that allow the harmful bugs to "survive and thrive," as the disease progresses.

These complex communities of bacteria, known as the microbiome, are altered in cirrhosis—where healthy liver tissue is replaced by scar tissue—preventing the liver from functioning properly.

The condition has no cure, affects quality of life, reduces life expectancy and may require liver transplantation, but not all people with cirrhosis are suitable for such treatment. In the UK, every year there are more than 10,000 deaths due to cirrhosis, and the cost to the NHS of liver disease exceeds £2 billion.

A key driver of cirrhosis complications and mortality is infection. Clinicians and scientists increasingly believe many of these infections are influenced by changes in the microbiome not only in the gut, but also from the mouth. This theory has been tested in a new study co-led by teams at King's College London, the Roger Williams Institute of Liver Studies and King's College Hospital.

The study is published in the Journal of Hepatology.

Increased harmful bacteria and reduced healthy bacteria

Using advanced DNA sequencing techniques, the mouth and gut microbiome of people with cirrhosis of different stages was shown to have increased harmful bacteria and reduced healthy bacteria. As cirrhosis worsened, so did the levels of harmful bacteria that were shown to have properties (called "virulence factors") that allow them to "survive and thrive" in people with cirrhosis.

Harmful bacteria move from the mouth to the gut—and vice versa

The microbiome was further altered in cirrhosis as there was less difference between the bacteria in the mouth compared to the gut—in healthy people, the bacterial colonies vary greatly between each location. This suggests that in cirrhosis, the bacteria move from the mouth to the gut, or vice versa, and in doing so can disrupt the gut wall and other key functions needed to maintain health. As people with cirrhosis got sicker, the degree of overlap between bugs in the mouth and gut grew.

Antimicrobial resistance and the need for targeted antibiotics

Critically, the harmful bacteria in patients with advanced cirrhosis were also shown to have far more genes that make them resistant to antibiotics, which can make treatment less effective. This may have a significant impact on the effectiveness of current treatments when cirrhosis patients are admitted to hospital and are often given a blanket course of general antibiotics, even if it is not certain they have an infection. This is because for every hour that someone with cirrhosis has an infection and is not given antibiotic treatment, their risk of death increases by 10%.

However, this blanket use of antibiotics can further harm the microbiome, sometimes without resolution of the infection, and can make these bacteria more antibiotic resistant. This highlights the need for better diagnostics to confirm whether there is an infection present and what is causing it, as well as the need for more effective treatments to prevent infections in the first place.

Scientists from across King's College London, including at the Faculty of Life Sciences & Medicine and Faculty of Dentistry, Oral & Craniofacial Sciences, came together to compare outcomes of 100 patients enrolled in this study, led by the Liver Unit at King's College Hospital. This included those with mild cirrhosis and severe cirrhosis—who were compared with healthy people.

Dr. Vishal Patel, Reader in Hepatology at The Roger Williams Institute of Liver Studies, King's College London and a clinician scientist based at King's College Hospital, said, "This research highlights how changes in the microbiome play a key role in worsening cirrhosis, especially as multidrug-resistant infections become more common. We showed that a greater overlap of bacteria in the mouth and gut, along with increased virulence and resistance genes, are closely related to clinical outcomes—especially for those people with more advanced cirrhosis.

"These insights suggest that personalized microbiome-based treatments could help improve outcomes for people with advanced chronic liver disease, including measures to improve oral health. This work also highlights the need for more rapid and accurate ways of diagnosing infections in our cirrhosis patients, so we can better use existing antibiotics."

Co-author Dr. Saeed Shoaie, researcher at the Centre for Host-Microbiome Interactions, King's College London, said, "By analyzing the oral-gut microbiome, our study traces antibiotic-resistant bacteria in cirrhosis. This will help improve diagnosis, surveillance, and personalized treatment strategies.

"This could be combined with AI to identify key resistance patterns, enabling specific, targeted antibiotic use."

Professor Philip Newsome, Director of the Roger Williams Institute of Liver Studies and King's Health Partner's Centre for Translational Medicine, said, "This is an important study that moves us one step closer to personalizing treatment for people with chronic liver disease—manipulating the microbiome represents an exciting opportunity for future therapies."

More information: Sunjae Lee et al, Oral-gut microbiome interactions in advanced cirrhosis: characterisation of pathogenic enterotypes and salivatypes, virulence factors and antimicrobial resistance, Journal of Hepatology (2024). DOI: 10.1016/j.jhep.2024.09.046

Provided by King's College London