A study finds that oral–gut translocation of collagenase-producing bacteria underpins the well-known association between microbiome perturbations and advanced chronic liver disease (ACLD) in humans. Importantly, Jin et al. detected oral microbial dysbiosis even in patients with compensated ACLD, and both oral and faecal dysbiosis worsened with the stage of liver disease, suggesting that oral dysbiosis precedes similar changes in the gut.

Experiments in mice with CCl₄-induced liver and gut fibrosis confirmed that oral administration of patient-derived prtC⁺ Veillonella and Streptococcus inoculates worsens both gut barrier dysfunction (indicated by plasma levels of fatty acid binding protein 2 (FABP2)) and fibrotic disease severity compared with CCl₄ alone. Immunofluorescence studies showed that gut epithelia from prtC-exposed mice exhibited disrupted tight-junction architectures with cytoplasmic relocation of the tight junction proteins E-cadherin and occludin. These findings suggest that oral–gut translocation of collagenase-producing bacterial strains might promote ACLD progression by inducing gut barrier disruption, which could lead to further microbial translocation along the gut–liver axis (the leaky gut hypothesis) that exacerbates liver and intestinal fibrosis. Thus, targeting the oral microbiome might have a role in preventing ACLD progression.