A recent study published in Nature Microbiology, conducted by research teams from King's College London and the Technical University of Munich, indicates that oral bacteria may colonize the gut in individuals with advanced chronic liver disease (ACLD). This phenomenon, termed "oral-gut translocation," is associated with the progression of the disease and is reported to contribute to the weakening of the gut barrier and the induction of liver fibrosis.
Background on Advanced Chronic Liver Disease
Advanced chronic liver disease affects millions globally and is responsible for over two million deaths annually. Current treatments primarily focus on managing complications, with limited therapies available to slow or prevent disease progression. Previous research has identified associations between ACLD and disruptions in the gut microbiome, suggesting a potential role for bacteria typically found in the mouth to colonize the gut.
Study Design and Key Findings
The study involved the analysis of saliva and stool samples from 86 ACLD patients at King's College Hospital. Researchers observed significant changes in both the gut and oral microbiomes as liver disease progressed. While bacterial communities in different body sites are typically distinct in healthy individuals, the study found that in patients with liver disease, the oral and gut microbiomes became increasingly similar with advancing disease stages.
Specific bacterial strains, including Veillonella and Streptococcus species, were identified as translocating from the mouth to the gut. This oral-gut translocation was noted to be more prevalent and pronounced in later stages of ACLD. The pattern of increased oral bacteria in the gut, which also carried higher levels of antimicrobial resistance genes and virulence factors, was specific to ACLD patients and not observed in control groups with severe sepsis but without liver disease.
Mechanism of Disease Progression
The research identified a specific mechanism through which these translocating bacteria may influence gut and liver health. A key factor was the presence of the prtC gene in these bacteria. This gene enables the production of collagenase, an enzyme that degrades collagen, a crucial component in maintaining the integrity of the gut barrier.
The breakdown of collagen by these enzymes may compromise the gut barrier. A weakened barrier can increase the entry of bacteria and their products into the bloodstream, potentially reaching the liver and other organs. This process is believed to contribute to further inflammation, scarring (fibrosis), and organ dysfunction in ACLD patients. Experiments conducted in a mouse model for liver disease further supported this hypothesis, demonstrating that introducing these bacteria from human patients exacerbated gut barrier damage and worsened liver fibrosis.
Diagnostic and Therapeutic Implications
The study highlights several potential implications for the diagnosis and treatment of ACLD:
- Biomarker Potential: Higher levels of the
prtCgene in stool samples were strongly associated with more severe chronic liver disease. TheprtCgene's ability to distinguish ACLD patients from healthy individuals was found to be comparable to existing clinical diagnostic tools. This suggestsprtCcould serve as a reliable microbial biomarker, potentially aiding in earlier identification of high-risk patients. - New Therapeutic Strategies: The findings suggest that targeting oral-to-gut translocation could lead to novel therapeutic approaches. These strategies might include:
- Protecting or restoring the gut barrier.
- Modulating the oral microbiome.
- Inhibiting collagenase activity.
Researchers are actively exploring these avenues with the aim of developing new treatments that could slow or prevent the progression of advanced chronic liver disease and reduce associated complications.