Analysis of intestinal microbiota and barrier function in chronic renal failure and therapeutic strategy

• Project/Area Number: 17K09722
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kawasaki Medical School
• Principal Investigator: Satoh Minoru 川崎医科大学, 医学部, 准教授 (70449891)
• Co-Investigator(Kenkyū-buntansha): 長洲 一 川崎医科大学, 医学部, 講師 (40412176)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 慢性腎不全 / 腸内細菌 / 腸管バリア / ディフェンシン / 腎不全 / Rスポンディン / 尿毒素 / 腸管透過性 / 細菌 / 腎臓病 / 腸管

Outline of Final Research Achievements

We hypothesized, "Chronic kidney disease impaied the intestinal barrier function by a change of microbial flora". We analyzed using CKD model mice the change of the enterobacterial flora, urine toxin production, and intestinal tract barrier function accompanied with the renal failure progress.Our studies have revealed that aggravation of the enterobacterial flora caused the increase of the inflammatory cytokines, and significant disruption of intestinal barrier function in different models of CKD. The increased uremic toxin in intestinal tract made as invasion into blood. In addition, we cleared that uremic toxin-indoxyl sulfate decreases intestinal antimicrobial peptides defensins which induce gut microbiome alteration in CKD, which are contribute to the loss of intestinal barrier function in CKD.

Academic Significance and Societal Importance of the Research Achievements

慢性腎不全の状態では腸管バリア機能が破綻し、尿毒素物質吸収が増加していることが明確にできた。また、腎不全でなぜ腸内細菌が悪化するかの原因として、ディフェンシン低下関与していることも判明した。ディフェンシンを増加させることで腸内細菌を改善し、腸管バリア機能を改善する可能性がある。

Research Products

• [Presentation] 腸管バリアの破綻と腸腎連関 (2019)
  • Author(s): 佐藤 稔
  • Organizer: 第62回日本腎臓学会学術総会
• [Presentation] The association of microbiota alteration and intestinal barrier function in chronic renal failure mice. (2018)
  • Author(s): Minoru Satoh, Seiji Itano,Yuji Sogawa, Yoshisuke Haruna, Kengo kidokoro, Hajime Nagasu, Tamaki Sasaki, Naoki Kashihara
  • Organizer: ISN Frontiers Meetings 2018
  • Int'l Joint Research
• [Presentation] Uremic toxin decreases intestinal defense peptides and barrier functions in chronic renal failure mice. (2018)
  • Author(s): Minoru Satoh, Seiji Itano, Megumi Kondo, Yoshihisa Wada, Hiroyuki Kadoya, Tamaki Sasaki, Naoki Kashihara.
  • Organizer: ASN KIDNEY WEEK 201