Prediction of drug-induced liver injury by gut microbiota response and its therapeutic development

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06643
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Sanoh Seigo 和歌山県立医科大学, 薬学部, 准教授 (00552267)
• Co-Investigator(Kenkyū-buntansha): 古武 弥一郎 広島大学, 医系科学研究科(薬), 教授 (20335649) ; 太田 茂 和歌山県立医科大学, 薬学部, 教授 (60160503)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腸内細菌 / 薬物性肝障害

Outline of Final Research Achievements

In this study, the pharmaceutical that were confirmed to disrupt the gut microbiota were administered to mice, suggesting that it alters the expression of genes related to liver function. On the other hand, we could find the endogenous substances among the intestinal bacterial metabolites that may affect liver function. In the future, we may be able to explain the mechanism of hepatotoxicity by the intestinal tract (intestinal bacteria)-liver interaction although it is necessary to take into account the species difference between mice and humans using humanized mice.

Free Research Field

衛生薬学

Academic Significance and Societal Importance of the Research Achievements

本研究を通して、薬物投与による腸内細菌環境の変化、それに伴う腸内細菌代謝物の変化が、腸管－肝臓の臓器連動のかく乱につながり、肝機能に影響を与える可能性が示唆された。今後の検討によって、動物モデルやヒトにおいて、薬物性肝障害に関わる特徴的な腸内細菌叢カタログを決定、さらにはカギとなる腸内細菌代謝産物を同定することにより、精度の高い薬物性肝障害の臨床診断指標の構築や新規治療薬の開発に貢献できるものと期待される。