ファミリアル・アデノマトス・ポリポシスの患者は,腫瘍発生性細菌を含む大腸のバイオフィルムを持っています
Christine M Dejea1,2, Payam Fathi1,2,3, John M Craig4
1Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA.
まとめ
Escherichia coliや Bacteroides fragilisのような特定の腸内細菌は,遺伝性大腸がん (CRC) の癌前病変と関連しています. これらのバクテリアは 腫瘍の成長を加速させる毒素を産生します
科学分野:
- 微生物学
- 腫瘍学
- 胃腸内科
背景:
- 腸内微生物群の変化は,散発性大腸がん (CRC) で一般的です.
- 遺伝性CRCにおけるがん前病変に関連した特定の微生物群はほとんど不明である.
- ファミリアルアデノマトス・ポリポシス (FAP) の患者は,生命の初期に良性の前駆体病変 (ポリプ) を発症する.
研究 の 目的:
- ファミリアルアデノマトス・ポリポシス (FAP) の患者の結腸内粘膜に関連する微生物群を調査する.
- 遺伝性大腸がんの初期段階における特定の細菌とその毒素の存在と役割を決定する.
主な方法:
- FAP患者と健康な人の結腸粘膜の分析
- バクテリアのバイオフィルム,特にEscherichia coliとBacteroides fragilisの特定
- オンコトキシンをコードする遺伝子の定量化:コリバクチン (*clbB*) と *Bacteroides fragilis* トキシン (*bft*).
- 腫瘍に罹患しやすいマウスを使った実験モデルで,E. coliと腸毒性B. fragilisが共存した.
主要な成果:
- FAP患者の大腸内膜には,主に*Escherichia coli*と*Bacteroides fragilis*という不規則な細菌のバイオフィルムが確認された.
- コリバクチン (*clbB*) と *Bacteroides fragilis* 毒素 (*bft*) の遺伝子は,健康な個体と比較して,FAP患者で著しく濃縮された.
- 両方のバクテリアで共存したマウスは インタールイキン17の増加,DNAの損傷,腫瘍の発症の速さ,単一のバクテリア株のマウスの死亡率の上昇を示した.
結論:
- 結腸の早期の腫瘍病変と特定の腫瘍発生性細菌との間には関連性がある.
- *E. coli* と腸毒性B. fragilis* の併用は,腫瘍毒素の産生と炎症による大腸内新生を促す可能性があります.
- これらの発見は,腸内微生物群と遺伝性大腸がんの病原性との潜在的な関連を強調しています.
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