Oral Pathobionts Aggravate NAFLD Through Modulation of Gut Dysbiosis

Objectives: Periodontal disease increases the risk of various diseases including non-alcoholic fatty liver disease (NAFLD). However, precise mechanisms for this connection have not been elucidated. Here, we show that gut dysbiosis induced by orally administered Porphyromonas gingivalis implicates in the deterioration of NAFLD pathology.
Methods: C57BL/6 mice were orally administered with vehicle only, P. gingivalis or Prevotella intermedia and subsequently fed choline-deficient, high-fat diet (CDAHFD60). The gut microbial communities were analyzed by pyrosequencing the 16S ribosomal RNA genes. Serum metabolites were analyzed using nuclear magnetic resonance (NMR)-based metabolomics coupled with multivariate statistical analyses. Gene expression profile of the liver was analyzed by DNA microarray.
Results: CDAHFD60 feeding induced hepatic steatosis and combined bacterial administration further aggravated NAFLD pathology with increased fibrosis. Gene expression analysis of the liver revealed that genes involved in the inflammation, ER-stress, fibrosis, circadian rhythms, and carcinogenesis, all of which are implicated in the NAFLD pathology, were perturbed with distinctive expression profile by different bacteria. These differences could be due to quantitative and qualitative difference in the influx of gut bacterial products because serum endotoxin level, composition of gut microbiota, and serum metabolite profile was different between P. intermedia and P. gingivalis.
Conclusions: Taken together, swallowed periodontopathic bacteria aggravate NAFLD pathology, likely due to dysregulation of gene expression by inducing gut dysbiosis and subsequent influx of gut bacteria and/or bacterial products into the liver.