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

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17586
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kyushu University
• Principal Investigator: NOGUCHI HIROSHI 九州大学, 大学病院, 助教 (70844364)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 移植免疫 / 臓器移植 / 腸内細菌叢 / 歯周病

Outline of Final Research Achievements

Immunosuppressive therapy is used to treat rejection in organ and tissue transplantation, but excessive suppression can lead to fatal infections. There are individual differences in rejection, and the involvement of gut microbiota has been identified as a factor. In this study, skin grafts were performed on mice with altered gut microbiota caused by periodontal bacteria and compared to normal mice to investigate the effect on transplantation immunity. The results showed that mice with altered gut microbiota had altered short-chain fatty acids in the gut and immune cells in the blood spleen, which significantly prolonged the number of days of skin graft survival. This suggests that gut microbiota may be the cause of individual differences in transplant immunity, which may lead to the individualization of future immunosuppressive therapies.

Free Research Field

膵臓・腎臓移植外科

Academic Significance and Societal Importance of the Research Achievements

臓器や組織移植における拒絶反応に対しては免疫抑制療法が行われるが、抑制が過剰になると致死的な感染症を惹起する可能性がある。また拒絶反応には個人差があり、その要因として腸内細菌叢の関与が指摘されている。この研究では、歯周病菌による腸内細菌叢の変化を引き起こしたマウスに皮膚移植を行い、正常マウスと比較することで移植免疫に与える影響を調査した。結果、腸内細菌叢を変化させたマウスでは腸内の短鎖脂肪酸や血液脾臓中の免疫細胞に変化がおきており、皮膚移植の生着日数が有意に延長した。これにより、腸内細菌叢が移植免疫における個人差の原因となる可能性が示唆され、今後の免疫抑制療法の個別化につながる可能性がある。