2023 Fiscal Year Final Research Report

Heme oxygenase/carbon monoxide-mediated intestinal modulation for the development of gas molecule drugs

Research Project

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Project/Area Number	20K08292
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 53010:Gastroenterology-related
Research Institution	Kyoto Prefectural University of Medicine
Principal Investigator	Tomohisa Takagi 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (70405257)
Co-Investigator(Kenkyū-buntansha)	内藤裕二京都府立医科大学, 医学(系)研究科(研究院), 教授 (00305575) 内山和彦京都府立医科大学, 医学(系)研究科(研究院), 講師 (50298428) 堅田和弘京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60593910)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	Heme Oxygenase-1 / 一酸化炭素 / Bach1 / 潰瘍性大腸炎 / Paraprevotella
Outline of Final Research Achievements	Based on the fact that dextran sulphate (DSS)-induced enteritis is suppressed in Bach1-deficient mice (mice with high expression of Heme Oxygenase-1 (HO-1)) compared to wild-type mice, it has been shown that DSS-induced enteritis was suppressed in wild-type mice transplanted with the intestinal environment of Bach1-deficient mice (HO-1-high expressing mice). Furthermore, the administration of Paraprevotella clara, which was identified as one of the intestinal bacteria showing predominance in the HO-1 high-expressing environment, suppressed intestinal inflammation, and was also found to be a significantly reduced species in patients with ulcerative colitis. It was considered to be a promising candidate bacterium as an anti-inflammatory bacterium.
Free Research Field	消化器内科学
Academic Significance and Societal Importance of the Research Achievements	Bach1欠損マウス（Heme Oxygenase-1(HO-1)高発現マウス）を用いて、一酸化炭素（Carbon monoxide: CO）高産生環境下での腸炎抑制効果を明らかにするとともに、この腸内環境形成に関与する腸内細菌叢としてParaprevotella claraを同定したことは本領域における重要な知見となった。さらに、Paraprevotella claraは日本人潰瘍性大腸炎患者で有意に減少している菌種であることを確認しており、抗炎症性細菌として有望な候補菌であると考えられ、新たな治療手段として期待される研究成果と考えられた。