Oral Microbiota Impact on Liver Disease Progression

The oral cavity harbours a diverse microbial community whose imbalance, or dysbiosis, can extend beyond local periodontal disease to influence systemic health, notably liver pathology. Pathogenic bacteria such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans may translocate via the digestive tract or bloodstream, triggering gut microbiota alterations, increased intestinal permeability and endotoxaemia. This cascade promotes hepatic inflammation, lipid accumulation and oxidative stress, driving progression from simple steatosis to nonalcoholic steatohepatitis (NASH) and ultimately fibrosis. Key mediators include bacterial virulence factors that activate hepatic stellate cells through transforming growth factor-β and Smad/ERK pathways, alongside systemic inflammatory cytokines and reactive oxygen species. Recognition of a mouth–gut–liver axis underscores the global significance of oral health in preventing and managing chronic liver disease. Emerging strategies aim to modulate oral and gut microbiota to interrupt this axis, offering novel avenues for early intervention and risk stratification in populations at high risk of fatty liver and its complications.

Research from Nature Portfolio

Recent studies have shown that experimental infection with Aggregatibacter actinomycetemcomitans in murine models alters gut microbial composition and glucose metabolism, exacerbating hepatic steatosis and insulin resistance in fatty liver settings. In parallel, investigations into odonto­genic Porphyromonas gingivalis infection in high-fat diet-induced NASH models demonstrate that bacterial dissemination and secreted enzymes such as gingipain activate hepatic stellate cells via TGF-β1-dependent Smad and ERK signalling. This activation promotes collagen deposition and fibrotic remodelling, linking oral pathogen exposure directly to liver fibrosis. Together, these mechanistic insights substantiate a direct contributory role for oral pathobionts in accelerating liver inflammation and matrix expansion.

Oral Microbiota Impact on Liver Disease Progression publication trend

The graph below shows the total number of articles in oral microbiota impact on liver disease progression across all publications each year (not limited to Nature Index journals).

Technical terms

Oral microbiota: The complex community of microorganisms inhabiting the oral cavity, including bacteria, fungi and viruses.

Dysbiosis: An imbalance in microbial communities that disrupts host–microbe homeostasis and promotes disease.

Nonalcoholic fatty liver disease (NAFLD): A spectrum of liver conditions characterised by excessive fat accumulation in hepatocytes without significant alcohol consumption.

Nonalcoholic steatohepatitis (NASH): An advanced form of NAFLD featuring inflammation, hepatocellular injury and varying degrees of fibrosis.

Hepatic stellate cells (HSCs): Liver pericytes that, when activated by injury or inflammation, transdifferentiate into collagen-secreting myofibroblasts.

Endotoxaemia: The presence of endotoxins, such as lipopolysaccharide, in the bloodstream, often arising from increased intestinal permeability.

References

1. Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis. npj Biofilms and Microbiomes (2024).
2. Involvement of Periodontal Disease in the Pathogenesis and Exacerbation of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis: A Review. Nutrients (2023).
3. Periodontal pathogenic bacteria, Aggregatibacter actinomycetemcomitans affect non-alcoholic fatty liver disease by altering gut microbiota and glucose metabolism. Scientific Reports (2017).
4. Periodontal disease–related nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: An emerging concept of oral‐liver axis. Periodontology 2000 (2021).
5. Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver. PLOS ONE (2015).
6. Odontogenic infection by Porphyromonas gingivalis exacerbates fibrosis in NASH via hepatic stellate cell activation. Scientific Reports (2020).