Analysis of the effects of dysbiosis due to high fructose diet on liver inflammation, carcinogenesis, and cancer progression

• Project/Area Number: 17K09432
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kagoshima University
• Principal Investigator: Tanoue Shiroh 鹿児島大学, 医歯学域鹿児島大学病院, 助教 (70611820)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Dysbiosis / フルクトース / 発癌 / 脂肪肝 / 肝炎 / 肝細胞癌

Outline of Final Research Achievements

Hepatocellular carcinoma is a typical inflammatory carcinogenesis that occurs against the background of chronic hepatitis and cirrhosis. In this study, we investigated the effects of abnormal intestinal flora composition (Dysbiosis) on fatty liver and hepatocarcinogenesis, and on the intestinal barrier function using fatty liver model mice due to fructose and excess lipid intake. In the fucurtose overdose group, intestinal permeability was increased and concentration of Lipopolysaccharide (LPS) in the portal vein tended to be high, and intrahepatic precancerous lesions were increased. These results suggested that the intestinal barrier dysfunction caused by the difference of diet content might influence hepatocarcinogenesis.

Academic Significance and Societal Importance of the Research Achievements

本研究によってフルクトース過剰摂取など欧米型食事といった食事習慣により引き起こされる腸内細菌異常Dysbiosis によって脂肪肝を背景とした肝癌の発育・進展に及ぼす影響が明らかとなった。今後肝癌に代表される炎症性発癌機構の解明につながるのみならず、発癌抑制を目指した新たな治療法の分子基盤となることが期待される。