Study on dysbiosis of intestinal flora caused by bacteriophage

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08845
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Sekizuka Tsuyoshi 国立感染症研究所, 病原体ゲノム解析研究センター, 室長 (40462775)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ファージ / 腸内細菌 / 多様性 / 細菌叢破綻

Outline of Final Research Achievements

An efficient and convenient method of recovering phage from feces was devised in this study, and the genomic sequence of the novel bacteriophage was determined. Gut microbiota and phageome of patients with ulcerative colitis (UC) given antibiotic combination therapy were compared between both before and after treatment using metagenomic analysis. Comparison of the metagenomic data suggested that major population of several bacteria showed a negative correlation between before treatment in the active stage and remission after treatment. In addition, it is suggested that the composition of the phageome between active and remission stages in each patient was drastically changed and there was no similarity between active and remission stages of all patients. Liquid phage infection assay was performed against feces of a healthy person with extracted phage from feces of patients with UC in active stages, however, proliferation of phage extracted from feces of UC patients was not confirmed.

Free Research Field

細菌学、ゲノム生物学

Academic Significance and Societal Importance of the Research Achievements

潰瘍性大腸炎(UC)患者の腸内細菌叢では、活動期と寛解期において共通して増減する細菌種が存在する一方、ファージの組成には共通項は認めらず、その組成は個人ごとにおいても治療前後で大きく異なっていた。UCでは細菌叢の破綻が関与し、健常な細菌叢に戻すことで寛解に向かうことが本研究でも明らかとなったが、ファージの組成も大きく変化することが強く示唆された。腸管内の細菌およびファージ組成の変化を共に注視することで、寛解維持の状態を把握できる可能性が予想され、侵襲性の少ない、メタゲノム解析手法を用いた経過観察を行うための基盤が作成できたものと思われる。