Impact of butyrate-producing bacteria in the gut on fatty liver diseases.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K11002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Tokai University
• Principal Investigator: KAGAWA Tatehiro 東海大学, 医学部, 教授 (30245469)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 脂肪肝 / 酪酸菌 / 腸内細菌

Outline of Final Research Achievements

Fatty liver is a hepatic phenotype of metabolic syndrome and effective therapy is awaited. In this study we analyzed the microbiomes and long-term prognosis in patients with histologically diagnosed fatty liver diseases and investigated the effect of Clostridium butyricum on hepatic fat deposition in rodent fatty liver models. We found that the prognosis was significantly worse in patients with non-alcoholic steatohepatitis (NASH) and those with type 2 diabetes mellitus. The occurrence of liver-related events (hepatocellular carcinoma, hemorrhage from esophageal or gastric varices, ascites, hepatic encephalopathy, liver failure) was observed more frequently in patients with type 2 diabetes mellitus and those with advanced fibrosis, and those with milder steatosis. The proportion of butyrate-producing bacteria was reduced in the gut of fatty liver patients. Administration of Clostridium butyricum mitigated hepatic fat accumulation in rodent fatty liver models.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

本研究では脂肪肝の長期予後並びに、脂肪肝における酪酸産生菌の意義を検討した。脂肪肝の予後に糖尿病の合併が大きく関与していることが明らかとなり、予後を改善するには糖尿病のコントロールが重要であることが判明した。また、脂肪肝患者の腸内細菌叢において酪酸産生菌が減少していること、齧歯類の脂肪肝モデルで、酪酸菌の投与が肝の脂肪蓄積を軽減することが明らかとなり、今後、酪酸菌が脂肪肝の治療薬として使用できる可能性が示唆された。