New research co-led by King's College London, King's College Hospital NHS Foundation Trust and the Technical University of Munich, in collaboration with the Quadram Institute (Norwich), has found that some bacteria originating in the mouth can move to the gut and cause damage to the gut barrier that may accelerate chronic liver disease.
The study, published in Nature Microbiology, shows that in advanced chronic liver disease (ACLD) - where scarring of the liver (fibrosis) stops the liver from working properly (cirrhosis), potentially leading to liver failure - bacteria originating in the mouth appear to colonise the gut.
The researchers pinpointed the process by which these oral bacteria (1) weaken the gut barrier, encouraging other harmful gut bacteria and their products to enter the bloodstream, increasing infection risk, and (2) drive further liver damage by inducing fibrosis.
By analysing saliva and stool samples from 86 patients with ACLD recruited from within the liver service at King's College Hospital, researchers identified specific bacterial strains, particularly species of Veillonella and Streptococcus, that were moving from the mouth into the gut. This process, known as 'oral-gut translocation', was not only more common and more pronounced in later stages of ACLD, but also appeared to be actively contributing to disease progression.
What distinguished the translocating bacteria was the presence of a gene called 'prtC', which enables the production of a collagenase-an enzyme that breaks down the type of collagen responsible for maintaining the integrity of the gut barrier.
When this barrier weakens, bacteria and inflammatory molecules can enter the bloodstream, reach the liver and other organs, and drive further inflammation, scarring, and wider organ dysfunction through the gut-liver axis.
The researchers found that higher levels of prtC in stool samples were strongly associated with more severe chronic liver disease. Notably, prtC distinguished ACLD patients from healthy individuals with an accuracy comparable to clinical diagnostic tools already used in hospital settings.
Given that ACLD is often diagnosed late, a reliable microbial biomarker such as this could represent a major advance.
Growing similarity between the mouth and gut
This latest research builds on earlier work led by Dr Vishal Patel whose research group is based at the Roger Williams Institute of Liver Studies (RW-ILS) at King's College London, which found that people with chronic liver disease experience dramatic changes in the types and functions of bacteria in both the gut and the mouth. Understanding the links between cirrhosis and the gut-liver-brain axis is a priority area in the RW-ILS, and that study was the first to comprehensively map the degree of overlap between oral and gut microbiomes in ACLD, as well as interrogate the impact of this on developing risks of antimicrobial resistance.
The researchers saw that as ACLD worsened, the composition of the saliva and gut microbiomes became increasingly similar.
Patients in the most severe stages of ACLD showed a striking over-representation of oral bacteria in the gut, at significantly higher levels than in healthy people, and these bacteria harboured much higher levels of antimicrobial resistance genes and virulence factors, which allow bugs to 'survive and thrive' and evade immune responses.
Importantly, this pattern was not observed in a comparison group of patients with severe sepsis who had similar medical complexity but no underlying liver disease, highlighting that these changes are specific to ACLD.
A potential new way to diagnose and prevent liver failure
ACLD affects millions worldwide and causes more than two million deaths each year. Current treatments largely focus on complications, and there are no widely available therapies that reliably slow or prevent disease progression.
Because prtC arises early and strongly in the disease course, testing for it could help identify high-risk patients well before symptoms develop, guide decisions around monitoring and earlier initiation of preventative approaches, and support evaluation of treatments in future clinical trials, the researchers say.
Targeting oral-to-gut translocation could also open the door to new therapeutic strategies aimed at protecting the gut barrier, modulating the oral microbiome, or inhibiting collagenase activity. This is an area the researchers are now actively exploring, in collaboration with dental experts.
The liver clinical and scientific communities have long recognised the importance of the 'gut-liver axis' in people with cirrhosis. What we are now beginning to see is that the mouth is an integral part of this too. This is an exciting step towards truly understanding how the oral and gut microbiomes contribute to chronic liver disease progression. More importantly, it brings us closer to new diagnostic and therapeutic approaches for a disease that urgently needs them.
Dr Vishal C Patel, Adjunct Reader in Hepatology at King's College London, Consultant Hepatologist at King's College Hospital NHS Foundation Trust, and co-senior author of the paper.
"Our study highlights how bioinformatic analyses can be leveraged to computationally predict host-microbial interactions, which can be further investigated to generate new mechanistic insights into disease processes. Importantly, oral-gut translocation has been implicated in several inflammatory and autoimmune diseases and our study provides a powerful framework to investigate microbiome functionality in these diseases as well," said Professor Melanie Schirmer, co-lead author from Technical University of Munich
"This research exemplifies the kind of discovery-to-impact work we champion at the Roger Williams Institute of Liver Studies - bridging fundamental microbiology with clinical application to address major unmet need in liver disease. The potential for early diagnosis through a microbial biomarker, combined with new therapeutic targets, could transform outcomes for the millions of people worldwide living with advanced chronic liver disease," said Professor Philip Newsome, Director of the Roger Williams Institute of Liver Studies and King's Health Partners Centre for Translational Medicine.
