Multifaceted pathophysiologic evaluation of sepsis targeting the intestinal microflora and development of novel therapeutic strategies

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03782
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Hiroshima University
• Principal Investigator: SHIME NOBUAKI 広島大学, 医系科学研究科(医), 教授 (00260795)
• Co-Investigator(Kenkyū-buntansha): 今井 由美子 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 ヘルス・メディカル微生物研究センター, 副センター長 (50231163)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 敗血症 / 腸管 / TSPO / 臓器不全 / 心筋症 / 脳症 / Zonulin

Outline of Final Research Achievements

We analyzed clinical information and blood samples from septic patients and investigated the significance of various markers and obtained the following results: 1) low levels of zonulin, a marker of intestinal permeability, are associated with worse prognosis; 2) TSPO, a mitochondrial protein, is decreased in septic patients; 3) GDF-15, an indicator of mitochondrial dysfunction, is increased in septic cardiomyopathy patients; and 4) lipidomics analysis revealed that lysophosphatidylcholine 16:0 and 18:0 are significantly decreased in septic patients compared to healthy controls, correlating with severity of illness. In animal studies, a mouse model was established to examine behavioral abnormalities as a long-term effect of sepsis, and the association of TSPO were confirmed.

Free Research Field

集中治療医学，救急医学，感染症学

Academic Significance and Societal Importance of the Research Achievements

腸内細菌叢、腸管上皮細胞、免疫系は相互に作用し合う。敗血症患者における腸管機能は近年主要な介入標的として着目されている。敗血症における腸管関連の新しい特定代謝産物の変化を同定し、免疫賦活効果や腸管透過性など腸管機能の改善効果、さらには中枢神経系や心臓など敗血症性多臓器不全に及ぼす影響を明らかにできれば、これまで特異的な治療法のなかった敗血症に伴う臓器不全症に対する新規治療法につながる基礎的知見を提供できる。