Changes in gut microbiota induced by oral pathobiont deteriorate the pathology of non-alcoholic fatty liver disease

Periodontitis increases the risk of non-alcoholic fatty liver disease (NAFLD). However, the precise mechanisms are unclear. Here, gut dysbiosis induced by orally administered Porphyromonas gingivalis, a representative periodontopathic bacterium, was implicated in the deterioration of NAFLD pathology. C57BL/6 mice were administered with the vehicle, P. gingivalis or Prevotella intermedia, with weaker periodontal pathogenicity, followed by feeding on a choline-deficient, high fat diet (CDAHFD60). CDAHFD60 feeding induced hepatic steatosis, and combined bacterial administration further aggravated NAFLD pathology with increased fibrosis. Liver gene expression analyses revealed that genes involved in the NAFLD pathology were perturbed with distinctive expression profiles induced by different bacteria. These differences may be due to quantitative and qualitative differences in the influx of gut bacterial products because the serum endotoxin level, gut microbiota composition, and serum metabolite profile caused by ingested P. intermedia and P. gingivalis were different. These findings provide insights into mechanisms linking periodontitis and NAFLD. Effect of oral administration of P. intermedia and P. gingivalis on the liver gene expression profile was mesured in high fat diet-fed mice. Mice were divided into 4 groups ( regular chow, no bacteria (n=3), high fat diet, sham (n=4), high fat diet, P. intermdia (n=4), high fat diet, P. gingivalis (n=5)). Bacteria were administered 2 times aweek for 3 weeks nd high fat diet was fed for 2 weeks.