Periodontal disease can induce dysbiosis, a compositional and functional alteration in the microbiota. Dysbiosis induced by periodontal disease is known to cause systemic inflammation and may 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). For 6 weeks, the Pg group orally received Pg while the control group orally received phosphate-buffered saline solution. After that, both groups received allogenic skin grafts. 16 s rRNA analysis of feces revealed that oral administration of Pg significantly increased three short chain fatty acids (SCFAs) producing genera. SCFA (acetate and propionate) levels were significantly higher in the Pg group (p = 0.040 and p = 0.005). The ratio of regulatory T cells, which are positively correlated with SCFAs, to total CD4+ T cells in the peripheral blood and spleen was significantly greater (p = 0.002 and p < 0.001) in the Pg group by flowcytometry. Finally, oral administration of Pg significantly prolonged skin graft survival (p < 0.001) and reduced pathological inflammation in transplanted skin grafts. In conclusion, periodontal pathogen-induced intestinal dysbiosis may affect transplant immunity through increased levels of SCFAs and regulatory T cells. (198 words).

Pancreas transplants from expanded criteria donors are performed widely in Japan because there is a shortage of brain-dead donors. However, the effectiveness of this strategy is unknown. We retrospectively studied 371 pancreas transplants to evaluate the possibility of pancreas transplantation from expanded criteria donors by the Pancreas Donor Risk Index (PDRI). Patients were divided into five groups according to quintiles of PDRI values (Q1–Q5). The 1-year pancreas graft survival rates were 94.5% for Q1, 91.9% for Q2, 90.5% for Q3, 89.3% for Q4, and 79.6% for Q5, and were significantly lower with a lower PDRI (p = 0.04). A multivariate analysis showed that the PDRI, donor hemoglobin A1c values, and pancreas transplantation alone significantly predicted 1-year pancreas graft survival (all p &lt; 0.05). Spline curve analysis showed that the PDRI was incrementally associated with an increased risk of 1-year graft failure. In the group with a PDRI ≥ 2.87, 8/56 patients had graft failures within 1 month, and all were due to graft thrombosis. The PDRI is a prognostic factor related to the 1-year graft survival rate. However, pancreas transplantation from high-PDRI donors shows acceptable results and could be an alternative when the donor pool is insufficient.

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Background: Periodontitis is known as a risk for many systemic diseases. We investigated the association between oral health status and outcomes after living donor kidney transplantation. Methods: We retrospectively analyzed 57 patients who had undergone living donor kidney transplantation and preoperative oral care at our institution. We divided patients into two groups by preoperative percentage of tooth sites with bleeding on probing (BOP), followed by comparing the cumulative incidence of infection (cytomegalovirus infection, biopsy-proven BK nephropathy, urinary tract infection, and any other infection requiring hospitalization) and biopsy-proven rejection including borderline changes after transplantation between the two groups. Results: The cumulative incidence of patients with BOP of 2% or more was significantly higher (180 days and 1 year; 49.2% and 55.5%, respectively) than patients with BOP<2% (180 days and 1 year; 22.8% and 29.8%, respectively; P=0.018). Cox hazard regression analysis showed that preoperative BOP was a statistically significant risk factor for the incidence of infection after transplantation in univariate (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.00-1.06; P=0.019) and multivariate analysis (HR, 1.03; 95% CI, 1.00-1.06; P=0.013). Rejection-free survival of patients with BOP of 2% or more was higher than patients with BOP<2%, although it was not statistically significant (P=0.286). Conclusions: Our data suggest that preoperative BOP is a risk factor for infection after transplantation, especially within 180 days.

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.