An orally administered oral pathobiont and commensal have comparable and innocuous systemic effects in germ-free mice.

ABSTRACT

BACKGROUND AND OBJECTIVES: We recently proposed a novel mechanism linking periodontitis and systemic diseases, in which orally administered Porphyromonas gingivalis affects gut microbiota composition and subsequently leads to systemic inflammation. However, the mechanism by which P. gingivalis generates systemic effects from the gut is unknown. MATERIAL AND METHODS: Six-week-old germ-free mice were orally administered with either an oral pathobiont P. gingivalis or an oral commensal Lactobacillus salivarius twice a week for 5 weeks. Control mice were administered with vehicle only. Alveolar bone resorption was evaluated histologically. The expression profile of various genes was analyzed in gingival tissue, liver, small intestine and large intestine using real-time polymerase chain reaction. Sera were analyzed for antibody, endotoxin and interleukin (IL)-6 levels. Antibody levels were also analyzed for culture supernatant of cells from mesenteric lymph nodes and spleens. A proportion of T-helper 17 and Treg in the cells from mesenteric lymph nodes and spleens was analyzed by flow cytometry. The level of IL-6 and IL-17 in the cell culture supernatants was analyzed by enzyme-linked immunosorbent assay. RESULTS: P. gingivalis administration did not induce alveolar bone resorption. Although P. gingivalis elicited systemic antibody response in germ-free mice, unlike in specific pathogen-free mice, P. gingivalis did not induce an inflammatory response in gingiva, liver and intestinal tissue, or alter the proportion of T-helper 17 and Treg. However, IL-6 and IL-17 productions were significantly elevated and tended to be elevated, respectively, in the cells from mesenteric lymph nodes of P. gingivalis-administered mice. Interestingly, the expression of IL-10 and tight junction protein in the gingiva and intestine, respectively, was significantly upregulated in P. gingivalis-treated mice. Administration of L. salivarius elicited almost similar effects as P. gingivalis. CONCLUSION: The oral pathobiont P. gingivalis did not induce any detectable pathogenic changes or any major host responses when administered to germ-free mice. There may be indirect mechanisms for gut-mediated systemic effects by P. gingivalis.