内容紹介
Summary
Recent developments in techniques of metabologenomics have given a better understanding the association of gut microbiota with various diseases. Gut microbiota has a strong impact on host immunostasis and homeostasis of gut function for maintaining the health condition. Dysbiosis leads to an increase in bacterial populations that stimulate tumorigenesis, and contributes to epithelial carcinogenesis and tumor progression by altering metabolic properties(such as bile acid and butyric acid)and inflammatory process. Inflammation aid the bacterial translocation into the neoplastic tissue, which in turn promotes production of inflammatory cytokines subsequently leading to tumor growth. The colonic microbiota such as enterotoxigenic Bacteroides fragilis(ETBF)may also promote colorectal cancer by stimulating exaggerated immune responses via Th17 cells. Dysbiosis caused by a deficiency of the NLRP6 inflammasome promotes cancer development via interleukin-6(IL-6)-induced epithelial proliferation. Emerging data suggest that certain groups of bacteria might promote whereas others might protect against colon cancer. Indeed, Fusobacterium nucleatum(F. nucleatum)seems to play a central role in the tumor microenvironment as its abundance correlates with cancer progression as well as the dysbiotic tumor microbiota composition including Bacteroides and Prevotella species. Moreover, gut microbiota not only plays a key role in carcinogenesis but also influences the efficacy and toxicity of cancer immunotherapy, especially immune checkpoint inhibitors by targeting the programmed death receptor 1(PD-1)and the cytotoxic T lymphocyte antigen 4(CTLA-4).
要旨
メタボロゲノミクスによる腸内細菌叢の解析により,腸内細菌叢と各種疾患との関連性が解明されつつある。腸内細菌叢は,宿主に対して免疫制御や腸管機能の恒常性維持において重要な役割を果たしている。dysbiosisは発癌に関連する腸内細菌が増加し,胆汁酸や酪酸などの代謝産物の変化や炎症を惹起することにより上皮の発癌および腫瘍の形成に関与すると考えられている。たとえばenterotoxigenic Bacteroides fragilis(ETBF)などのTh17細胞の分化誘導を来す菌の増加は免疫応答を刺激し,NOD-like receptor family pyrin domain containing 6(NLRP6)インフラマソームの欠乏により誘発されたdysbiosisはinterleukin(IL)-6起因性上皮増殖を来し,いずれも癌の発生を促進する。大腸癌の発生や予防と関連する腸内細菌に関するデータが蓄積されつつあるが,なかでもFusobacterium nucleatum(F. nucleatum)はBacteroidesやPrevotella科とともに発癌における中心的な役割を担っていると考えられている。さらに腸内細菌叢は,発癌のみならず癌免疫療法,特にprogrammed cell death 1(PD-1)および細胞傷害性Tリンパ球抗原4(CTLA-4)をターゲットとした免疫チェックポイント阻害薬の有効性と有害事象にも影響を及ぼすことが指摘されている。
目次
Recent developments in techniques of metabologenomics have given a better understanding the association of gut microbiota with various diseases. Gut microbiota has a strong impact on host immunostasis and homeostasis of gut function for maintaining the health condition. Dysbiosis leads to an increase in bacterial populations that stimulate tumorigenesis, and contributes to epithelial carcinogenesis and tumor progression by altering metabolic properties(such as bile acid and butyric acid)and inflammatory process. Inflammation aid the bacterial translocation into the neoplastic tissue, which in turn promotes production of inflammatory cytokines subsequently leading to tumor growth. The colonic microbiota such as enterotoxigenic Bacteroides fragilis(ETBF)may also promote colorectal cancer by stimulating exaggerated immune responses via Th17 cells. Dysbiosis caused by a deficiency of the NLRP6 inflammasome promotes cancer development via interleukin-6(IL-6)-induced epithelial proliferation. Emerging data suggest that certain groups of bacteria might promote whereas others might protect against colon cancer. Indeed, Fusobacterium nucleatum(F. nucleatum)seems to play a central role in the tumor microenvironment as its abundance correlates with cancer progression as well as the dysbiotic tumor microbiota composition including Bacteroides and Prevotella species. Moreover, gut microbiota not only plays a key role in carcinogenesis but also influences the efficacy and toxicity of cancer immunotherapy, especially immune checkpoint inhibitors by targeting the programmed death receptor 1(PD-1)and the cytotoxic T lymphocyte antigen 4(CTLA-4).
要旨
メタボロゲノミクスによる腸内細菌叢の解析により,腸内細菌叢と各種疾患との関連性が解明されつつある。腸内細菌叢は,宿主に対して免疫制御や腸管機能の恒常性維持において重要な役割を果たしている。dysbiosisは発癌に関連する腸内細菌が増加し,胆汁酸や酪酸などの代謝産物の変化や炎症を惹起することにより上皮の発癌および腫瘍の形成に関与すると考えられている。たとえばenterotoxigenic Bacteroides fragilis(ETBF)などのTh17細胞の分化誘導を来す菌の増加は免疫応答を刺激し,NOD-like receptor family pyrin domain containing 6(NLRP6)インフラマソームの欠乏により誘発されたdysbiosisはinterleukin(IL)-6起因性上皮増殖を来し,いずれも癌の発生を促進する。大腸癌の発生や予防と関連する腸内細菌に関するデータが蓄積されつつあるが,なかでもFusobacterium nucleatum(F. nucleatum)はBacteroidesやPrevotella科とともに発癌における中心的な役割を担っていると考えられている。さらに腸内細菌叢は,発癌のみならず癌免疫療法,特にprogrammed cell death 1(PD-1)および細胞傷害性Tリンパ球抗原4(CTLA-4)をターゲットとした免疫チェックポイント阻害薬の有効性と有害事象にも影響を及ぼすことが指摘されている。