Mechanisms of metabolic dysfunction-associated steatohepatitis progression induced by periodontitis and therapeutic strategies.

BACKGROUND: Multiple factors contribute to the progression of metabolic dysfunction-associated steatohepatitis (MASH), which can lead to severe conditions, such as liver cirrhosis and hepatocellular carcinoma. Therefore, identifying the risk factors, developing targeted treatment strategies, and implementing preventive measures are essential to combat this disease. Periodontitis is a highly prevalent infectious disease worldwide, and it is a significant risk factor for the progression of systemic diseases, including MASH. However, therapeutic strategies for MASH are limited, particularly those that address the potential translocation of periodontal pathogens. In this review, the contribution of periodontitis to the progression of MASH is explored, and its potential for providing new therapeutic insights is discussed.

HIGHLIGHT: Recent studies, including in animal models and using clinical observations, suggest that Porphyromonas gingivalis translocates to the liver and promotes hepatic inflammation and fibrotic progression in MASH. In vitro studies have shown that gingipains, which are trypsin-like proteases produced by P. gingivalis, proteolytically activate protease-activated receptor 2 in hepatocytes and hepatic stellate cells. Gingipains contribute to fibrosis by inducing production of transforming growth factor β, which activates hepatic stellate cells. Gingipain inhibitors have the potential to suppress activation of stellate cells induced by P. gingivalis infection.

CONCLUSION: Targeting P. gingivalis, not only in the oral cavity, but also in the liver, may be essential for suppressing MASH-associated inflammation and fibrosis. Gingipain inhibitors may effectively suppress MASH by eliminating the effects of translocated P. gingivalis. A deeper understanding of this odontogenic-hepatic axis will facilitate the development of targeted therapies.