Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota

TLDR

Periodontitis is linked to metabolic disorders such as type 2 diabetes, atherosclerosis, and non‑alcoholic fatty liver disease, yet direct evidence connecting oral bacteria to systemic inflammation is lacking. The study tests whether swallowing periodontopathic bacteria disrupts the gut microbiota, triggering metabolic endotoxemia that drives metabolic disease. Mice were orally gavaged with Porphyromonas gingivalis and subsequently assessed for gut microbial shifts, insulin resistance, glucose intolerance, and tissue inflammation. Oral P.

Abstract

Abstract Periodontitis has been implicated as a risk factor for metabolic disorders such as type 2 diabetes, atherosclerotic vascular diseases and non-alcoholic fatty liver disease. Although bacteremias from dental plaque and/or elevated circulating inflammatory cytokines emanating from the inflamed gingiva are suspected mechanisms linking periodontitis and these diseases, direct evidence is lacking. We hypothesize that disturbances of the gut microbiota by swallowed bacteria induce a metabolic endotoxemia leading metabolic disorders. To investigate this hypothesis, changes in the gut microbiota, insulin and glucose intolerance and levels of tissue inflammation were analysed in mice after oral administration of Porphyromonas gingivalis , a representative periodontopathogens. Pyrosequencing revealed that the population belonging to Bacteroidales was significantly elevated in P. gingivalis -administered mice which coincided with increases in insulin resistance and systemic inflammation. In P. gingivalis -administered mice blood endotoxin levels tended to be higher, whereas gene expression of tight junction proteins in the ileum was significantly decreased. These results provide a new paradigm for the interrelationship between periodontitis and systemic diseases.