The findings of the team led by Prof. Melanie Schirmer provide starting points for new therapies for advanced chronic liver disease.
Photo Credit: Astrid Eckert / TUM
Scientific Frontline: "At a Glance" Summary
- Main Discovery: Specific oral bacteria were found to translocate to and colonize the gut in patients with chronic liver disease, where they actively contribute to disease progression rather than acting as passive bystanders.
- Mechanism of Action: These translocated bacteria express genes encoding collagen-degradation enzymes (collagenases) that damage the intestinal barrier, allowing bacterial pathogens to leak into the liver and exacerbate fibrosis.
- Methodology: The study combined comparative microbiome sequencing of patient samples with in vivo mouse experiments, demonstrating that introducing these specific oral strains into mice directly worsened gut barrier damage and liver condition.
- Key Observation: While healthy individuals maintain distinct oral and gut microbiomes, patients with advanced liver disease exhibited nearly identical bacterial strains in both sites, indicating significant bacterial migration.
- Diagnostic Application: The presence and abundance of the specific gene responsible for collagen degradation in stool samples were identified as a reliable biomarker for distinguishing patients with liver disease from healthy individuals.
- Therapeutic Potential: These findings suggest that therapies targeting the oral microbiome or inhibiting microbial collagenase activity could restore gut barrier integrity and slow the progression of chronic liver disease.
Whether in the gut, mouth, or on the skin, the human body is colonized by bacteria. Most of them are beneficial and we find distinct microbial communities at different body sites. A team led by the Technical University of Munich (TUM) and King’s College London has now found strong evidence that bacteria from the mouth migrate to the gut in chronic liver disease and exacerbate the disease.
Each year, more than two million people die from advanced chronic liver disease (ACLD). Previous research has linked gut microbiome disruptions to this condition and suggested that bacteria typically found in the mouth may colonize the gut.
A new study published in Nature Microbiology now shows that identical bacterial strains occur in both the mouth and gut of patients with advanced chronic liver disease and also reveals a mechanism by which oral bacteria affect gut health. The researchers also found that this process coincides with worsening liver health.
Unusual similarity between oral and gut microbiome
Researchers analyzed bacterial populations in saliva and stool samples from 86 patients. The team found that both the gut and oral microbiome undergo significant changes as liver disease worsened, where changes of the oral microbiome were detectable already at earlier disease stages.
In healthy individuals, bacterial communities differ substantially between body sites. In patients with liver disease, however, oral and gut microbiomes became increasingly similar as the disease progressed and nearly identical bacterial strains were recovered from the mouth and gut of patients. “These strains are typically found in the mouth and are rarely present in the healthy gut. However, we observed increases in the absolute abundances of these oral bacteria in patients with advanced chronic liver disease. This strongly suggests that these bacteria translocate from the mouth and colonize the gut,” explains Melanie Schirmer, Professor of Translational Microbiome Data Integration at TUM.
Bacteria can damage the intestinal barrier
The team identified several oral bacterial species that colonized patients’ guts. They also found evidence that higher levels of these bacteria in stool samples were associated with damage to the intestinal barrier.
“To investigate this link, we performed a gene analysis,” says Shen Jin, one of the study’s first authors. “We discovered that these bacteria carry genes encoding collagen-degradation enzymes.” The team confirmed these enzymes were active by testing isolated bacteria from stool samples and synthesizing the enzyme. “Collagen breakdown can compromise the gut barrier, potentially allowing bacteria and bacterial products to reach other organs, such as the liver. We believe this may worsen the disease,” explains Aurelie Cenier, a doctoral researcher and co-first author.
Experiments in a mouse model for liver disease supported this hypothesis: introducing these bacteria from human patients exacerbated gut barrier damage and worsened liver fibrosis.
Implications for diagnosis and treatment
“Our findings open potential new therapeutic strategies for people with advanced chronic liver disease. Protecting or restoring the gut barrier could help slow disease progression. Targeting the oral microbiome offers a way to positively influence the course of the disease and prevent clinical complications,” says Dr. Vishal Patel from King’s College London.
The study also suggests a new diagnostic approach. The team examined the bacterial gene involved in collagen degradation in more detail. Its abundance in stool samples could serve as a future disease marker. In the study, this marker reliably distinguished sick individuals from healthy ones.
Reference Material: What Is: Human Microbiome
Published in journal: Nature Microbiology
Title: Microbial collagenase activity is linked to oral–gut translocation in advanced chronic liver disease
Authors: Shen Jin, Aurelie Cenier, Daniela Wetzel, Bethlehem Arefaine, Mar Moreno-Gonzalez, Marilena Stamouli, Merianne Mohamad, Mariia Lupatsii, Emilio Ríos, Sunjae Lee, Ane Zamalloa, Shilpa Chokshi, Adil Mardinoglu, Saeed Shoaie, Naiara Beraza, Vishal C. Patel, and Melanie Schirmer
Source/Credit: Technische Universität München
Reference Number: mcb011526_01
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