Effects of periodontal pathogen–induced intestinal dysbiosis on transplant immunity in an allogenic skin graft model

Abstract

Periodontal disease can alter the intestinal microbiota. Harmful changes to the microbiota are called “dysbiosis” and can induce systemic inflammation and affect transplant immunity. Here we examined the effects of periodontal disease–related intestinal dysbiosis on transplant immunity using a mouse model of allogenic skin graft in which the mice were orally administered the periodontal pathogen Porphyromonas gingivalis (Pg). The Pg group received Pg orally for 6 weeks, while the control group received phosphate-buffered saline solution orally for 6 weeks. Both groups received allogenic skin grafts. We compared levels of short-chain fatty acids (SCFAs) (fecal microbiome metabolites) and the proportion of regulatory T cells (Tregs) out of total CD4 + T cells before skin grafting. We performed the allogenic skin transplantation and also assessed skin graft survival. SCFA (acetate and propionate) levels were significantly higher (p = 0.040 and p = 0.005), the ratio of Tregs to total CD4 + T cells in the peripheral blood and spleen was significantly greater (p = 0.002 and p < 0.001) than in the control group. Oral administration of Pg significantly prolonged skin graft survival (p < 0.001). Periodontal pathogen–induced intestinal dysbiosis may affect transplant immunity through increased levels of SCFAs and Tregs.