Drug discovery for Diabetic Nephropathy through altering gut microbiota community

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K20604
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Tohoku University
• Principal Investigator: ABE Takaaki 東北大学, 医工学研究科, 教授 (80292209)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 糖尿病性腎臓病 / 腸内細菌 / ミトコンドリア / フェニル硫酸

Outline of Final Research Achievements

Researchers have shown that phenyl sulfate (PS) is produced from tyrosine by intestinal bacteria in diabetes mellitus and causes glomerular damage and albuminuria, and that in a cohort of diabetic patients, albuminuria is exacerbated and prognosis is worse at 2 years in patients with high blood PS levels, and proposed a new treatment concept for DKD in which lowering blood PS concentration decreases albuminuria and improves renal function (Kikuchi K. Nat. Commun ;10: 1835, 2019). In this study, we investigated the mechanism of PS production in diabetic patients at the enzymatic, bacterial, and animal levels.
We aimed to elucidate the mechanisms of PS production in diabetic patients at the enzymatic, bacterial, and animal levels, and to develop new DKD therapies to reduce blood PS concentrations.

Free Research Field

腎臓病学

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎臓病（DKD）は本邦で1000万人を超える糖尿病患者の約20％に発症し導入透析患者の4割を占める。そのため、DKDを発症して重症化する糖尿病患者を早期に選別して積極的に治療介入する方法は透析患者を減らし、莫大な医療費の削減効果をもたらす。現在のところDKDに特異的な治療法はない。厳格な血糖管理とレニンーアンジオテンシン系阻害剤による血圧管理といった一般の糖尿病・高血圧患者の治療が有効とされ行われるが、なお、DKDの発症と進行は十分に阻止できていない。本研究により糖尿病性腎臓病の減少がもたらされることにより透析導入患者数を減少させ医療費の削減がもたらされる可能性がある。