腸道微生態失調與大腸直腸癌之關聯

The Relationship between Gut Dysbiosis and Colorectal Cancer

曹書儀(Shu-Yi Tsao) ； 張育霖(Yu-Lin Chang) ； 陳進生(Jin-Sheng Chen) ； 黃文威(Wen-Wei Huang)

《內科學誌》 28卷3期 (2017/06) Pp. 160-167

https://doi.org/10.6314/JIMT.2017.28(3).06

摘要

大腸直腸癌發生率與死亡人數一直居高不下。大腸直腸癌是累積多項基因及表徵基因(epigenetic) 改變，使正常大腸黏膜轉變成腺癌。除遺傳傾向外，環境與生活模式亦影響大腸直腸癌的發生。許多研究發現腸道微菌叢(gut microbiota) 與人體健康維持及疾病發生有關，其中與腸道相關的有腸炎、大腸直腸腺瘤及癌。近年來應用16S 核糖體RNA 定序，對微菌的研究成果突飛猛進，多種微菌被發現與大腸直腸癌的發生有關。當正常腸道微菌叢受到不良改變，即腸道微生態失調(gut dysbiosis) 時，會增加發生大腸直腸癌風險，相關機轉為透過慢性發炎、毒素、有毒代謝物在大腸黏膜細胞內活化NF-kB 及STAT3 等訊號路徑，減少細胞凋亡，促進上皮細胞增生，生成大腸直腸瘜肉- 腺瘤- 腺癌；或產生活性化物質，破壞去氧核醣核酸(DNA)，造成基因毒性而致癌。運作過程可參考“細菌驅動– 伺機模式(bacterial driver-passenger model)＂：一些攝入腸道的細菌(驅動細菌(bacterial drivers))，具原致癌性質，造成上皮DNA 破壞，使大腸直腸癌發源；接著，伺機性(opportunistic) 細菌(伺機細菌(bacterial passengers)) 增生，使腫瘤發展。老化、環境及食物對大腸直腸癌發生的影響可能也與腸道微生態失調有關。透過補充益生菌、調整食物及運動有益於改善腸道微菌叢。全球對腸道微菌叢的研究方興未艾，將來可望應用它來防治大腸直腸癌，更進一步維繫全身健康。

關鍵字

腸道微菌叢(Gut microbiota) ； 大腸直腸癌(Colorectal cancer) ； 腸道微生態失調(Gut dysbiosis)

並列摘要

Colorectal cancer(CRC) is a common cancer and a leading cause of cancer deaths worldwide. CRC results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to CRC. Besides genetic predisposition, the environment and life style influence the genesis of CRC. Many researches discover the role of microbiota for keeping human health and the potential causal impact on some human diseases. Adversely alteration of gut ecosystem (gut dysbiosis) is frequently associated with increased susceptibility to many human diseases including colitis, colorectal adenoma and CRC. With 16S ribosomal RNA sequencing used to identify and classify bacteria, many studies for microbiota were developed in recent years. It is observed that gut dysbiosis can promote the onset and progression of CRC. The mechanism may be by chronic inflammation, genotoxin, toxic metabolites to active NF-kB and STAT3 signal pathway that decrease apoptosis, enhance development of colorectal polyp-adnoma-adenocarcinoma. Another pathway is increased reactive oxygen species causes genotoxity that promote oncogenesis. Using ＂Bacterial driver-passenger model＂ to elucidate the process: First, ＂bacterial drivers＂ drive the epithelial DNA damage that contributes to the initiation of CRC. Second, tumorigenesis induces intestinal niche alterations that favour the proliferation of opportunistic bacteria (＂bacterial passengers＂) that promote development of cancer. The effect of aging, environment and diet to promote CRC formation may be associated with gut dysbiosis. Probiotics, dietary adjustment and exercise have beneficial impact on gut microbiota. Prevention, screening and treatment for CRC with advance application of microbiota may be achieved in future.