| Project/Area Number |
22K16211
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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 53040:Nephrology-related
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| Research Institution | Chiba University |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Completed (Fiscal Year 2024)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2024: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 腸内細菌叢 / トリメチルアミンNオキシド（TMAO） / 骨髄由来免疫抑制細胞 / 慢性腎臓病(CKD) / 尿毒素物質 / 透析患者 / 慢性腎臓病 / 免疫 |
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| Outline of Research at the Start |
本研究は５段階で構成され，特定の腸内細菌が透析患者の病態へ及ぼす影響を明確にする.①検体収集：血液・糞便試料を収集【透析患者71例，健常31例】②測定：糞便試料のメタ16ｓ解析（明治製菓（株）との共同研究），血液中MDSCs測定．③解析：クラスター解析により近い腸内細菌組成をもつ患者グループを作成（図4），血中MDSCsの比較により免疫能低下に影響すると思われる菌種の候補を同定，候補とした腸内細菌叢を有意にもつ透析患者の感染症歴を検証．④裏付け実験：抗菌薬投与マウスを用いる，糞便移植は③で候補にした菌種を投与、⑤治療への転換：特定の細菌組成にする手段（食品,薬剤,便移植等）を動物実験で検証．
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| Outline of Final Research Achievements |
Changes in the intestinal flora (dysbiosis) can lead to the progression and complications of kidney disease. However, the specific characteristics of the flora in patients with renal failure are not fully understood, so the point of intervention is unclear. Therefore, we conducted a meta-16s analysis of feces collected from hemodialysis patients and healthy subjects in Chiba Prefecture. We found that the patient and healthy groups had significantly different compositions, with a higher number of bacterial species in the patient group compared to the healthy group, many of which were minor bacteria with an occupancy rate of less than 1%, and that the increase in the number of minor bacterial species resulted in a relative decrease in the intestinal bacteria that are predominant in Japanese people, such as Bifidobacterium.Furthermore, we demonstrated that the increased minority bacteria produced trimethylamine N-oxide, which correlated with cardiovascular complications.
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| Academic Significance and Societal Importance of the Research Achievements |
他国に比べ平均透析期間が長いとされる本邦でも，透析患者の5年生存率は60.8％，10年生存率は35.9％であり，生命予後は決して良好とはいえない．一般人口の死亡原因の１位が悪性腫瘍であるのに対し，透析患者は感染症や心血管合併症が上位を占めるためである．腸内環境の悪化を改善するような新たな食事指導の開発や薬物治療が明らかになれば、透析患者の生活の質改善だけでなく健康寿命の増進につながると期待される．
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