Development of a new renal therapy through Gut-renal axis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02932
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tohoku University
• Principal Investigator: ABE TAKAAKI 東北大学, 医工学研究科, 教授 (80292209)
• Co-Investigator(Kenkyū-buntansha): 大坪 和香子 東北大学, 農学研究科, 助教 (00598203) ; 倉永 英里奈 東北大学, 生命科学研究科, 教授 (90376591)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: CKD / 腸内細菌 / ミトコンドリア

Outline of Final Research Achievements

Chronic Kidney diseases associated with abnormal mitochondrial function (mitochondrial-related nephropathy) cause many pathological conditions, but there are no specific therapeutic drugs, and existing treatments have been the only option. The applicant has discovered MA-5, a novel synthetic indole compound that promotes ATP production. The reason why the plant hormone IAA, which is the precursor to MA-5, exists in the human body lies in intestinal bacteria. Human endosymbiont mitochondria and exosymbiont intestinal flora interact with each other through low-molecular compounds to regulate the health and lifespan of the human host. In order to elucidate the intestinal-kidney link, this research will elucidate the mutual regulatory network between mitochondria and intestinal flora, elucidate the effect of improving mitochondrial function, elucidate the mechanism by which kidney mitochondria are controlled from the intestines, and develop new treatments.

Free Research Field

腎臓

Academic Significance and Societal Importance of the Research Achievements

ヒトの腸内細菌叢は宿主の栄養や免疫制御を担い、CKD患者の腸内細菌叢は尿毒素産生や炎症を惹起して腎障害を増悪する「ディスバイオーシス」の状態にある。申請者はこの「腸腎連関」をCKD治療に応用する研究を世界に先駆けて推進し、新規下剤やSGLT2阻害薬、尿毒素合成酵素阻害薬などが腸内細菌叢を変化させ尿毒素の低減と腎機能改善をもたらすこと報告した。腸内細菌の代謝物を研究する事がミトコンドリア機能調節の新しいメカニズム解明に繋がり、最終的にミトコンドリア腎症の　治療に結付くと考え本申請に至った。