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Porhyromonas gingivalis , a causative bacterium of periodontitis, is implicated in the etiology of rheumatoid arthritis (RA), mainly because of expressing peptidyl arginine deiminase (PAD) that generates RA-related autoantigens. However, compared with other periodontopathic bacteria, the precise role of  P .  gingivalis  in RA is largely unknown. We found that orally administered  P .  gingivalis  changed the gut microbiome with concomitant elevation of serum endotoxin and inflammatory markers, and impairment of the gut barrier function. Based on findings showing a relationship between gut microbiota and RA, we investigated whether the change of gut microbiota induced by  P .  gingivalis  and  Prevotella intermedia , another periodontopathic bacterium without PAD, is associated with collagen-induced arthritis (CIA). DBA/1J mice were orally administered with or without bacteria followed by induction of CIA.  P .  gingivalis , but not  P .  intermedia , administration significantly aggravated arthritis with increased interleukin-17 levels in sera and culture supernatants, increased Th17 cell proportions among mesenteric lymphocytes, and a significant change in the gut microbiome. However,  P .  gingivalis  administration did not elevate the level of anti-citrullinated protein antibody. These results suggest a unique role of  P .  gingivalis  in the link between periodontitis and RA by affecting the gut immune system and the gut microbiota composition.

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Aggravation of collagen-induced arthritis by orally administered Porphyromonas gingivalis through modulation of the gut microbiota and gut immune system