Examination of treatment strategy for intractable C. difficile infection using the mouse C. difficile infection microbiota model

• Project/Area Number: 15K19593
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: Toho University
• Principal Investigator: YAMAGUCHI Tetsuo 東邦大学, 医学部, 助教 (10408239)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: CDI / プロバイオティクス / 腸内細菌叢 / 次世代シーケンサー / 次世代シークエンサー

Outline of Final Research Achievements

We investigated the effects of vancomycin, fidaxomicin, the probiotic Clostridium butyricum and the prebiotic lactoferrin on the intestinal microbiota in a mouse model with clindamycin induced intestinal dysbiosis followed by Clostridioides difficile inoculation. Composition of the intestinal microbiome was investigated by sequence and quantitative PCR analyses of bacterial 16S rRNA gene in faecal DNA. The class Clostridia formed a numerically smaller proportion of the microbiota in the model than in uninoculated mice. Both vancomycin and fidaxomicin treatment further decreased Clostridia in C. difficile-inoculated mice. Probiotic treatment increased the proportion of Clostridia in the microbiome, but C. difficile inoculation led to decreased gut microbiome diversity compared with uninoculated mice.

Academic Significance and Societal Importance of the Research Achievements

抗菌薬関連腸炎の中でもCDIは代表的な疾患であるが、近年、強毒型C. difficileが欧米を中心に問題となっており、その病態解析と適切な治療指針が求められている。特に腸内細菌叢の撹乱がCDI再発のリスクになるため、CDI発症時および抗CD薬投与時の腸内細菌叢の変化を明らかにすることは学術的・社会的に意義深い。使用する抗CD薬により細菌叢は異なり、プロバイオティクス投与による腸内細菌叢撹乱の予防効果が示唆された。現在、論文投稿準備中であり、情報を発信していく予定である。