2020 Fiscal Year Final Research Report

Elucidation of the molecular mechanism of hepatic encephalopathy and development of innovative treatment by intestinal bacterial flora profiling

Research Project

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Project/Area Number	18K08684
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Shinshu University (2019-2020) Kyushu University (2018)
Principal Investigator	soejima yuji 信州大学, 学術研究院医学系, 教授 (30325526)
Co-Investigator(Kenkyū-buntansha)	間野洋平九州大学, 大学病院, 助教 (10792244) 戸島剛男九州大学, 大学病院, 助教 (40608965) 本村貴志九州大学, 医学研究院, 共同研究員 (50719507) 吉住朋晴九州大学, 医学研究院, 准教授 (80363373) 原田昇九州大学, 大学病院, 講師 (80419580) 池上徹九州大学, 大学病院, 講師 (80432938) 伊藤心二九州大学, 大学病院, 助教 (90382423) 長尾吉泰九州大学, 大学病院, 助教 (70608968)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	生体肝移植 / 腸内細菌叢 / 短鎖脂肪酸 / 胆汁酸 / 便移植
Outline of Final Research Achievements	We investigated the composition of the gut microbiota in decompensated liver cirrhosis patients undergoing living donor liver transplantation and its relationship to the preoperative and postoperative course. We reported that the composition of the patients differed significantly from that of liver donors, and that portal venous pressure in the patients showed a significant positive correlation with phylum Bacteroidetes and fecal propionate levels. We also reported that the total bile acid, TCDCA, and GCDCA levels in the patients were significantly higher in serum bile acid analysis (all p<0.001), and that these values showed a significant positive correlation with the MELD score (p=0.022, p=0.023, and p=0.0087, respectively). We will continue to analyze the changes in bacterial flora before and after liver transplantation surgery and their clinical significance.
Free Research Field	消化器外科学
Academic Significance and Societal Importance of the Research Achievements	肝硬変はウイルス性肝炎などの原疾患の治療が可能な時期を過ぎると、対症療法が中心となり、特に非代償期においては肝移植以外に確立された治療法がない。また、肝移植後も感染症や拒絶反応といった合併症への不安を常に抱えている。我々の研究成果によって、非代償性肝硬変への腸内細菌叢の関与と肝移植による細菌叢の変化、ドナー細菌叢との関連が明らかになり、さらには便移植など非代償性肝硬変に対する新たな治療法の確立が期待でき、今後も研究を継続する予定である。