| Project/Area Number |
19K18028
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | Bariatric surgery / 腸内細菌叢 / 肝発癌 / 肥満 / 2型糖尿病 / NASH / Duodenal-jejunal bypass / DJB / Gut microbiota / 胆汁酸 / NKT細胞 |
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| Outline of Research at the Start |
これまでに研究者は、ラットDuodenal-jejunal bypass (DJB)モデルを用い「肥満症」に対する外科治療 (Bariatric surgery)は2型糖尿病・NASH改善効果を有し(JGH 2015)、その効果には腸内細菌叢Gut microbiotaの変化や胆汁酸が関与すると報告した(Surgery today 2017)。近年、腸内細菌叢(Clostridium減少)による二次胆汁酸の低下がNKT細胞を増加させ、肝癌抑制に寄与することが報告された(Science 2018)。本研究ではDJBによる腸内細菌叢の変化(Clostridium減少)は二次胆汁酸を低下させ、NKT細胞を増加させることで、肝発癌抑制・予防につながりうると仮説を立て検討を行うこととする。
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| Outline of Final Research Achievements |
The aim of this study was to investigate prevention of liver carcinogenesis in bariatric surgery. Methods; (1) Obese diabetic rats were divided into bariatric surgery (DJB) group and sham group. At postoperative 8 weeks, gut microbiome, gut inflammatory cytokines, claudin-1 and tumor counts in liver were investigated. (2) Obese diabetic rats were divided into bariatric surgery group (DJB) and sham group. After the operation, rats drunk DEN mixed water for 15 weeks. Tumor counts and size of the liver in two groups were investigated. Results; (1) DJB group showed increase of Proteobacteria. DJB group showed lower gut inflammation and maintenance of gut permeability. There was no tumor in the two groups. (2) Regarding liver tumor, there was no significant difference in the two groups. Conclusion; Bariatric surgery suppressed systemic inflammation through suppression of gut inflammation and maintenance of gut permeability. Bariatric surgery may prevent inflammation induced carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究を行う上で、DJBが腸内細菌叢microbiotaにどのように影響を及ぼしているのか、またこのmicrobiotaの変化がどのように2型糖尿病・NASH・肝発癌に影響しているかを検討することは極めて重要となってくるが、これが判明した際には、これまで内科的治療では到底改善できなかった肥満・糖尿病・NASHやそれらに関連する疾患や発癌に対する治療アプローチが一変する可能性がある。
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