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

Research Project

Project/Area Number 19K17387
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionHirosaki 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
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
KeywordsNAFLD / 腸内細菌叢 / エクオール / NASH / 脂肪肝 / Faecalibacterium / Slackia / MASLD / MASH / Lean NAFLD / アミノ酸 / Lean NAFLD / レプチン/アディポネクチン / βカロテン / 腸内細菌 / 非アルコール性脂肪肝 / 非アルコール性脂肪肝炎
Outline of Research at the Start

最近、NAFLD/NASHの病態に、腸内細菌叢と腸内代謝産物の異常が関与することが報告されている。しかし、NAFLD/NASH 発症には、多様な原因があり、従来の腸内環境の評価法では限界があり、一定の見解が得られていない。本研究は、追跡調査ができる1000名以上の大規模住民健診から、多項目に及ぶ NAFLD/NASH進展因子の調査を行う。それら因子の調整後に、腸内細菌叢の評価することでNAFLD/NASHの真の腸内環境の異常を明らかにする。腸内環境の解明により、原因菌に対するプロバイオティクスを開発し、NAFLD/NASHへの進展を予防を目指す。

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.

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。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (12 results)

All 2023 2022 2021 2020 2019

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Effect of Liver Fibrosis on Oral and Gut Microbiota in the Japanese General Population Determined by Evaluating the FibroScan?Aspartate Aminotransferase Score2023

    • Author(s)
      Sato Satoshi、Iino Chikara、Chinda Daisuke、Sasada Takafumi、Tateda Tetsuyuki、Kaizuka Masatoshi、Nomiya Hiroki、Igarashi Go、Sawada Kaori、Mikami Tatsuya、Nakaji Shigeyuki、Sakuraba Hirotake、Fukuda Shinsaku
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 17 Pages: 13470-13470

    • DOI

      10.3390/ijms241713470

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduced Equol Production and Gut Microbiota Features in Men With Lean Nonalcoholic Fatty Liver Disease2022

    • Author(s)
      Chikara Iino
    • Journal Title

      Am J Mens Health

      Volume: 4 Issue: 4 Pages: 0-0

    • DOI

      10.1177/15579883221115598

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of metabolic dysfunction-associated fatty liver disease using FibroScan, diet, and microbiota: A large cross-sectional study2022

    • Author(s)
      Tetsuyuki Tateda, Chikara Iino
    • Journal Title

      PLoS One

      Volume: 17 Issue: 11 Pages: 0-0

    • DOI

      10.1371/journal.pone.0277930

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatic Macrophages Express Melanoma Differentiation-Associated Gene 5 in Nonalcoholic Steatohepatitis2021

    • Author(s)
      Kawaguchi Shogo、Sakuraba Hirotake、Horiuchi Momone、Ding Jiangli、Matsumiya Tomoh、Seya Kazuhiko、Iino Chikara、Endo Tetsu、Kikuchi Hidezumi、Yoshida Shukuko、Hiraga Hiroto、Fukuda Shinsaku、Imaizumi Tadaatsu
    • Journal Title

      Inflammation

      Volume: 45 Issue: 1 Pages: 343-355

    • DOI

      10.1007/s10753-021-01550-8

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Changed Amino Acids in NAFLD and Liver Fibrosis: A Large Cross-Sectional Study without Influence of Insulin Resistance2020

    • Author(s)
      Takuma Hasegawa, Chikara Iino, Tetsu Endo, Kenichiro Mikami, Masayo Kimura, Naoya Sawada, Shigeyuki Nakaji, Shinsaku Fukuda
    • Journal Title

      Nutrients

      Volume: 12 Issue: 5 Pages: 1-8

    • DOI

      10.3390/nu12051450

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between serum β-carotene-to-retinol ratio and severity of hepatic steatosis in non-alcoholic fatty liver disease in Japan: A cross-sectional study2020

    • Author(s)
      Masayo Kimura, Kenichiro Mikami, Tetsu Endo, Masashi Matsuzaka, Naoya Sawada, Go Igarashi, Chikara Iino, Takuma Hasegawa, Kaori Sawada, Masataka Ando, Itoyo Tokuda, Hiroyuki Suganuma, Mai Matsumoto, Shigeyuki Nakaji, Shinsaku Fukuda
    • Journal Title

      Nutrition

      Volume: 3 Pages: 1-10

    • DOI

      10.1016/j.nut.2020.110984

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Leptin/adiponectin ratio correlates with hepatic steatosis but not arterial stiffness in nonalcoholic fatty liver disease in Japanese population2020

    • Author(s)
      Kenichiro Mikami, Tetsu Endo, Naoya Sawada, Go Igarashi, Masayo Kimura, Takuma Hasegawa, Chikara Iino, Hirofumi Tomita, Kaori Sawada, Shigeyuki Nakaji, Masashi Matsuzaka, Natalie J Torok, Shinsaku Fukuda
    • Journal Title

      Cytokine

      Volume: 126 Pages: 1-9

    • DOI

      10.1016/j.cyto.2019.154927

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significant decrease in Faecalibacterium among gut microbiota in nonalcoholic fatty liver disease: a large BMI- and sex-matched population study2019

    • Author(s)
      Chikara Iino, Tetsu Endo, Kenichiro Mikami, Takuma Hasegawa, Masayo Kimura, Naoya Sawada, Shigeyuki Nakaji, Shinsaku Fukuda
    • Journal Title

      Hepatology International

      Volume: 6 Issue: 6 Pages: 748-756

    • DOI

      10.1007/s12072-019-09987-8

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Characteristics of MASLD compared to NAFLD and MAFLD, and assessment of fibrosis2023

    • Author(s)
      飯野 勢
    • Organizer
      アジア太平洋肝臓学会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Lean NAFLDでのダイゼイン摂取における エクオール産生能と腸内細菌の特徴2022

    • Author(s)
      飯野 勢
    • Organizer
      日本消化器病学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 大規模調査によるNAFLDにおける腸内細菌叢の変化2019

    • Author(s)
      飯野 勢, 遠藤 哲, 福田 眞作
    • Organizer
      第105回日本消化器病学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] CHARACTERIZATION OF GUT MICROBIOTA IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE: A LARGE POPULATION-BASED STUDY2019

    • Author(s)
      Chikara Iino, Tetsu Endo, Daisuke Chinda, Shinsaku Fukuda
    • Organizer
      DDW2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2025-01-30  

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