Gut kidney axis in diabetic kidney disease

• Project/Area Number: 21K08224
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Kanazawa University
• Principal Investigator: Yasunori Iwata 金沢大学, 医学系, 教授 (90432137)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 糖尿病関連腎臓病 / 腸管環境 / 慢性腎臓病 / 急性腎障害 / 糖尿病性腎臓病 / 腸内細菌 / 腸管上皮機能 / 腎臓学 / 細菌学

Outline of Research at the Start

糖尿病性腎症の病態における、腸内細菌叢の攪乱と、腸管上皮のバリヤー破綻の意義を検討する。疾患を進展させる責任腸内細菌の同定を試み、代謝産物の病態への意義を検討する。また、生体側の腸管上皮細胞のバリヤー機能に着目する点も、本研究課題の特徴である。これらの研究を通して、腸管環境と末梢臓器の連関を明らかにし、新たな診断法、治療候補の創出を試みたいと考えている

Outline of Final Research Achievements

In recent years, it has become clear that the gut microbiota and its metabolites are involved in maintaining homeostasis in the body, and that dysbiosis of gut microbiota is involved in the onset and progression of various diseases. It has also been shown that the intestinal environment is deeply involved in the pathophysiology of kidney disease. We have clarified that intestinal bacterial cells are involved in the progression mechanism of diabetic kidney disease. In a mouse model of diabetic kidney disease, we showed that intestinal bacteria are translocated into the body due to leaky gut, resulting in chronic inflammation. This suggests that the intestinal epithelium may be a new therapeutic target for diabetic kidney disease.

Academic Significance and Societal Importance of the Research Achievements

本邦の慢性腎臓病患者は、約１３３０万人と推定されており、新たな国民病とも考えられている。治療手段はいまだ限られており、新規の病態解明や治療薬の開発が求められている。本研究課題で得られた知見は、糖尿病関連腎臓病の新たな病態と治療標的の可能性を示しており、将来的な臨床応用の基盤となる結果であると考えられる。

Research Products

• [Journal Article] Sex differences in risk factors for end‐stage kidney disease and death in type 2 diabetes: A retrospective cohort study. (2023)
  • Author(s): Oshima M, Iwata Y*, Toyama T, Kitajima S, Hara A, Sakai N, Shimizu M, Furuichi K, Haneda M, Babazono T, Yokoyama H, Iseki K, Araki S, Ninomiya T, Hara S, Suzuki Y, Iwano M, Kusano E, Moriya T, Satoh H, Nakamura H, Makino H, Wada T
  • Journal Title: J Diabetes Volume: 15 Issue: 3 Pages: 246-254
  • DOI: 10.1111/1753-0407.13367
  • Peer Reviewed / Open Access
• [Journal Article] Myocardin‐related transcription factor contributes to renal fibrosis through the regulation of extracellular microenvironment surrounding fibroblasts (2023)
  • Author(s): Yamamura Yuta、Sakai Norihiko、Iwata Yasunori、et al.
  • Journal Title: The FASEB Journal Volume: 37 Issue: 7
  • DOI: 10.1096/fj.202201870r
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Characterization of cytoskeletal and structural effects of INF2 variants causing glomerulopathy and neuropathy (2023)
  • Author(s): Ueda Hiroko、Tran Quynh Thuy Huong、Tran Linh Nguyen Truc、Higasa Koichiro、Ikeda Yoshiki、Kondo Naoyuki、Hashiyada Masaki、Sato Chika、Sato Yoshinori、Tsukaguchi Hiroyasu
  • Journal Title: Scientific Reports Volume: 13 Issue: 1 Pages: 12003-12003
  • DOI: 10.1038/s41598-023-38588-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association Between Risperidone Use and Kidney Function Decline in Patients with Schizophrenia: A Retrospective Cohort Study (2023)
  • Author(s): Oshima Megumi, Toyama Tadashi, Nakade Yusuke、et al.
  • Journal Title: Clinical Therapeutics Volume: 45 Issue: 9 Pages: 889-893
  • DOI: 10.1016/j.clinthera.2023.07.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Polar vasculosis is associated with better kidney outcome in type 2 diabetes with biopsy-proven diabetic kidney disease: A multicenter cohort study (2023)
  • Author(s): Shimizu M, Furuichi K, Toyama T, Yamanouchi M, Hoshino J, Kitajima S, Hara A, Iwata Y, Sakai N, Yuzawa Y, Kitamura H, Sato H, Shibagaki Y, Suzuki Y, Uesugi N, Ueda Y, Kohagura K, Samejima K, Tsuruya K, Nishi S, Nishino T, Makino H, Matsuo S, Ubara Y, Yokoyama H, Wada T
  • Journal Title: J Diabetes Investig Volume: 14(11) Issue: 11 Pages: 1268-1278
  • DOI: 10.1111/jdi.14059
  • Peer Reviewed
• [Journal Article] Intra-brain and plasma levels of L-Serine are associated with cognitive status in patients with CKD. Kid Dis (2023)
  • Author(s): 〇Iwata Y*, Nakade Y, Kinoshita M, Sabit H, Nakajima R, Furuichi K, Mita M, Nakane M, Sakai N, Kitajima S, Toyama T, Miyagawa T, Hara A, Shimizu M, Sato K, Oshima M, Nakagawa S, Yamamura Y, Ogura H, Koshino Y, Nakada M, Wada T.
  • Journal Title: Kidney Dis (Basel) . Volume: 9 Issue: 2 Pages: 118-129
  • DOI: 10.1159/000527798
  • Peer Reviewed / Open Access
• [Journal Article] Protective Effect of D-Alanine Against Acute Kidney Injury. (2022)
  • Author(s): Iwata Y, Nakade Y, Kitajima S, Yoneda-Nakagawa S, Oshima M, Sakai N, Ogura H, Sato K, Toyama T, Yamamura Y, Miyagawa T,Yamazaki H, Hara A, Shimizu M, Furuichi K, Mita M, Hamase K, Tanaka T, Nishida M, Muramatsu W, Yamamoto H, Shichino S, Ueha S, Matsushima K, Wada T.
  • Journal Title: Am J Physiol Renal Physiol. Volume: 322 Issue: 6 Pages: F667-F679
  • DOI: 10.1152/ajprenal.00198.2021
  • Peer Reviewed / Open Access
• [Journal Article] Intestinal Bacterial Translocation Contributes to Diabetic Kidney Disease. (2022)
  • Author(s): Linh HT, Iwata Y, Senda Y, Sakai-Takemori Y, Nakade Y, Oshima M, Nakagawa-Yoneda S, Ogura H, Sato K, Minami T, Kitajima S, Toyama T, Yamamura Y, Miyagawa T, Hara A, Shimizu M, Furuichi K, Sakai N, Yamada H, Asanuma K, Matsushima K, Wada T.
  • Journal Title: J Am Soc Nephrol. Volume: - Issue: 6 Pages: 1105-1119
  • DOI: 10.1681/asn.2021060843
  • Peer Reviewed / Open Access
• [Journal Article] Increased levels of oral Streptococcus-derived D-alanine in patients with chronic kidney disease and diabetes mellitus. (2022)
  • Author(s): Nakade Y, Iwata Y*, Sakai N, Mita M, Nakane M, Hamase K, Suda W, Toyama T, Kitajima S, Hara A, Shimizu M, Ogushi C, Furuichi K, Koshino Y, Morita H, Hattori M, Wada T.
  • Journal Title: Sci Rep Volume: 12 Issue: 1 Pages: 21773-21773
  • DOI: 10.1038/s41598-022-26175-1
  • Peer Reviewed / Open Access
• [Journal Article] TAS-Seq is a robust and sensitive amplification method for bead-based scRNA-seq. (2022)
  • Author(s): Shichino S, Ueha S, Hashimoto S, Ogawa T, Aoki H, Wu B, Chen CY, Kitabatake M, Ouji-Sageshima N, Sawabata N, Kawaguchi T, Okayama T, Sugihara E, Hontsu S, Ito T, Iwata Y, Wada T, Ikeo K, Sato TA, Matsushima K.
  • Journal Title: Commun Biol Volume: 5 Issue: 1 Pages: 602-602
  • DOI: 10.1038/s42003-022-03536-0
  • Peer Reviewed / Open Access
• [Journal Article] Rare toxin A-negative and toxin B-positive strain of Clostridioides difficile from Japan lacking a complete tcdA gene. (2022)
  • Author(s): Takemori-Sakai Y, Satou K, Senda Y, Nakamura Y, Otani H, Maekawa A, Oe H, Oshima M, Yoneda-Nakagawa S, Miyagawa T, Sato K, Ogura H, Mori M, Wada T, Sakai Y, Yutani M, Matsumura T, Fujinaga Y, Gabata T, Wada T, Iwata Y.
  • Journal Title: J Infect Chemother. Volume: 28 Issue: 5 Pages: 651-656
  • DOI: 10.1016/j.jiac.2022.01.015
  • Peer Reviewed / Open Access
• [Presentation] 膠原病合併妊娠の管理 (2023)
  • Author(s): 岩田恭宜
  • Organizer: 第67回日本リウマチ学会学術総会
  • Invited
• [Presentation] AKI to CKD (2023)
  • Author(s): 岩田恭宜
  • Organizer: 第66回日本腎臓学会学術総会
  • Invited
• [Presentation] MAVS Modulates Inflammation and Apoptosis in Renal Ischemia-Reperfusion Injury (2023)
  • Author(s): Taichiro Minamim Yasunori Iwata et al.
  • Organizer: ASN Kidney week 2023
  • Int'l Joint Research
• [Presentation] Crosstalk between gut microenvironment and kidney (2022)
  • Author(s): 岩田恭宜、中出祐介、和田隆志
  • Organizer: 第65回日本腎臓学会総会
  • Invited
• [Book] 腎臓内科 腎臓と免疫update (2022)
  • Author(s): 岩田恭宜
  • Total Pages: 8
  • Publisher: 科学評論社