Chronic Periodontitis and Non-Alcoholic Fatty Liver Disease: Recent Advances in Mechanisms of Association

Chronic periodontitis (CP) and non-alcoholic fatty liver disease (NAFLD) are increasingly prevalent worldwide. Although mechanisms remain incompletely defined, recent studies suggest a close association between these two diseases. This review systematically outlines potential links between periodontitis and NAFLD, emphasizing their pathological mechanisms and interactions within an oral-gut-liver framework.

We reviewed observational, interventional, and mechanistic studies evaluating associations between periodontal status/treatment and NAFLD-related outcomes, integrating evidence on dysbiosis, inflammatory mediators, microbial metabolites, oxidative stress, microRNA regulation, and gut barrier function.

Across epidemiological studies, periodontitis is associated with higher risk and greater severity of NAFLD. Mechanistically, oral dysbiosis, especially enrichment of oral pathobionts, is linked to hepatic steatosis and fibrosis. Translocation of microbial products and the resulting cytokine release drive systemic inflammation, impair gut barrier integrity, and induce hepatocellular injury. Microbial metabolites (such as short-chain fatty acids (SCFAs) and trimethylamine N-oxide (TMAO)) and oxidative stress contribute to metabolic dysregulation. Emerging evidence suggests that microRNAs (miRNAs) function as epigenetic regulators linking periodontal inflammation and bone remodeling to immune-metabolic pathways relevant to non-alcoholic fatty liver disease (NAFLD). However, direct evidence on whether treating periodontitis can improve NAFLD outcomes remains limited. Despite heterogeneity in study designs and diagnostic criteria, cumulative evidence supports periodontitis as a modifiable risk factor for the progression of NAFLD.

CP and NAFLD appear to be linked through systemic inflammation, dysbiosis, and metabolic disturbances. Future research should prioritize microbiome modulation, advance interdisciplinary care models, and develop personalized prevention and treatment strategies. Integrating oral and liver health within comprehensive management may provide new options for preventing and treating these frequently coexisting diseases.