| Project/Area Number |
18K08012
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Nagoya City University |
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Principal Investigator |
Inoue Takako 名古屋市立大学, 医薬学総合研究院(医学), 講師 (00431700)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 腸内フローラ / C型慢性肝炎 / 胆汁酸 / C型肝炎 / C型肝炎ウイルス / SVR後発癌 / 腸内細菌叢 / 発癌 |
|---|
| Outline of Final Research Achievements |
The fecal BAs composition, gut microbiota, and transcriptional analysis of the liver from chronic hepatitis C (CHC) patients was compared with that from healthy individuals.
CHC patients, even at earlier stages, showed BAs profiles distinct from healthy individuals, in which fecal deoxycholic acid (DCA) was significantly reduced and lithocholic acid or ursodeoxycholic acid became dominant. The decrease of fecal DCA was correlated with reduction of commensal Clostridiales and increase of oral Lactobacillales. Impaired biosynthesis of cholic acid (CA) was observed as a reduction of the transcription level of cytochrome P450 8B1 (CYP8B1), a key enzyme in CA biosynthesis.
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| Academic Significance and Societal Importance of the Research Achievements |
我々はC型慢性肝炎患者（CHC）の腸内フローラが病初期から変化し、病期進行につれて腸内フローラの破綻（dysbiosis）が顕著になることを報告した（Clin Infect Dis. 2018）。 本研究ではC型肝炎治癒後の発癌ハイリスク群囲い込みを可能にする腸内フローラモデルの実用化を目的とした。研究結果からHCV感染では肝内での胆汁酸代謝酵素の発現異常とdysbiosisが胆汁酸代謝異常を引き起こし、gut-liver axisを変化させることが分かった。またCHCと他の肝疾患ではその結果が異なることも証明することができた。
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