Microbial collagenase activity is linked to oral-gut translocation in advanced chronic liver disease

Area of Science:

• Microbiology
• Gastroenterology
• Immunology

Background:

• Microbiome alterations are linked to advanced chronic liver disease (ACLD).
• The specific mechanisms by which microbes contribute to ACLD pathogenesis remain largely unknown.
• Understanding these microbial contributions is crucial for developing novel therapeutic strategies.

Purpose of the Study:

• To investigate the role of oral-gut microbial translocation in ACLD.
• To identify specific microbial species and genes associated with ACLD.
• To explore the potential of these microbial factors as diagnostic biomarkers for ACLD.

Main Methods:

• Metagenomic analysis of paired saliva and fecal samples from ACLD patients and healthy/sepsis controls.
• Identification and abundance quantification of bacterial strains and specific genes.
• Inoculation of a mouse model of hepatic fibrosis with identified bacterial isolates.
• Measurement of fecal collagenase activity and gut barrier integrity.

Main Results:

• Highly similar oral and gut bacterial strains, including Veillonella and Streptococcus spp., were found in ACLD patients.
• These translocating bacteria possess a unique prtC gene encoding a collagenase-like proteinase.
• Fecal abundance of the prtC gene served as a robust ACLD biomarker (AUCPR = 0.91).
• Mouse models showed exacerbated hepatic fibrosis and gut barrier impairment upon inoculation with patient isolates.

Conclusions:

• Oral-gut microbial translocation, particularly of Veillonella and Streptococcus spp. carrying the prtC gene, is mechanistically linked to ACLD.
• The prtC gene and its encoded collagenase activity contribute to ACLD pathobiology.
• Fecal prtC gene abundance represents a promising biomarker for ACLD diagnosis.