Unraveling the Link between Gut Environment and Progression to NAFLD and NASH

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17387
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hirosaki University
• Principal Investigator: Iino Chikara 弘前大学, 医学部附属病院, 講師 (90814343)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: NAFLD / 腸内細菌叢 / エクオール / NASH / 脂肪肝 / Faecalibacterium / Slackia

Outline of Final Research Achievements

In a large-scale health examination involving over 1000 individuals, NAFLD was identified through Fibroscan measurements. Examination of the gut microbiota revealed significant alterations in diversity among NAFLD patients, with a notable decrease in the abundance of the butyric acid-producing bacterium Faecalibacterium. This reduction was indicative of increased intestinal permeability stemming from the breakdown of the Gut-Liver-axis and the consequent elevation of endotoxins of gut origin.
In male individuals with Lean NAFLD, characterized by a different metabolic mechanism from the obese type, there was an extremely low prevalence of equol producers, particularly with a significant decrease in Slackia within the gut microbiota. It was suggested that equol production capacity might be implicated in the onset of Lean NAFLD.

Free Research Field

腸内細菌叢

Academic Significance and Societal Importance of the Research Achievements

NAFLDでは腸内細菌叢の変化や破綻が起きており、特に善玉菌の酪酸酸性菌であるFaecalibacteriumの補充により、Gut-Liver axisの破綻を改善し、日本での罹患率が問題となっているNAFLDの進行の改善につながると考える。
また、女性ホルモン作用を示すエクオールは、エストロゲン作用によりメタボリックシンドロームに対して防護的に働く可能性が報告されている。エクオール産生に関わる腸内細菌叢のSlackiaの減少を認めるLean NAFLDはエクオール産生能が低く、NAFLDの発症に関わると考えられる。エクオールを摂取することで、脂肪肝の発症や改善が認められると考えられる。