The world's first analysis of the intestinal microbiota in IgA nephropathy and an attempt to elucidate the 'intestinal-renal relationship'

• Project/Area Number: 17K15784
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Juntendo University
• Principal Investigator: INOSHITA Hiroyuki 順天堂大学, 医学部, 非常勤助教 (80646117)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 腸内細菌叢 / 慢性腎臓病 / IgA腎症 / 粘膜免疫 / 腸内細菌叢解析 / 糖鎖異常 / ＩｇＡ腎症 / ＩｇＡ糖鎖異常 / 腸腎関連 / 制御性T細胞

Outline of Final Research Achievements

IgA nephropathy (IgAN) is the most common glomerulonephritis, and about 20-40% of the patients were developing end-stage kidney disease at 20 years after kidney biopsy. The pathogenesis of the disease is still unclear, although the full extent of the disease needs to be clarified as soon as possible.In the present study, we designed a study focusing on the 'intestinal-renal association' to elucidate the pathogenesis of IgAN. Since most cases of IgAN progress to chronic kidney disease, we first analyzed the intestinal microbiota of patients with chronic kidney disease to determine its distribution.In addition, serum cytokines associated with the intestinal microbiota have been measured in patients with chronic kidney disease and are currently being analyzed.

Academic Significance and Societal Importance of the Research Achievements

消化管粘膜にはおよそ100 兆個もの腸内細菌が極めて高密度で生息し，腸内細菌叢を形成している。腸内細菌叢は、粘膜関連リンパ組織(MALT)を成熟させ、分泌型IgA 抗体産生を促す他，免疫司令塔であるT 細胞を制御するなど、免疫システムの構築に貢献している。腸内細菌叢はIgANを含めた慢性腎臓病の発症・進展に深い関わりを持っていると推察されるが、慢性腎臓病患者の腸内細菌叢を解析した報告は、我々の知る限りなされていない。
我々の研究は慢性腎臓病患者の腸内細菌叢を16S rRNA 遺伝子解析により明らかにした上で免疫学的な解析を加えたのち、発症・進展の機序に迫るものである。