Comparison of human gut microbiota in control subjects and patients with colorectal carcinoma in adenoma: Terminal restriction fragment length polymorphism and next-generation sequencing analyses
Comparison of human gut microbiota in control subjects and patients with colorectal carcinoma in adenoma: Terminal restriction fragment length polymorphism and next-generation sequencing analyses
复制标题
DOI：
10.3892/or.2015.4398
复制
发表时间：
2016-01-01
期刊：
影响因子：
4.2
通讯作者：
Takase, Kojiro
中科院分区：
文献类型：
--
作者：
Kasai, Chika;Sugimoto, Kazushi;Takase, Kojiro
结直肠癌（CRC）是日本癌症相关死亡的第三大原因。结直肠癌的病因与许多因素有关，包括基因突变、饮食、生活方式、炎症，以及最近的肠道微生物群。然而，与crc相关的肠道微生物群在很大程度上仍未得到研究。本研究采用末端限制性片段长度多态性（T-RFLP）和下一代测序技术（NGS）对日本对照组和日本腺瘤癌患者的肠道微生物群进行了分析和比较。在结肠镜检查前，收集49名对照组、50名结肠腺瘤患者和9名结直肠癌患者（3/9为浸润性癌，6/9为腺瘤癌）的粪便样本；从每个粪便样本中提取DNA。根据T-RFLP分析，选取12例（对照组6例，腺瘤中癌组6例）；它们的样本被用于NGS和物种水平的分析。T-RFLP分析显示，对照组、腺瘤组和癌组之间细菌数量无显著差异。然而，NGS显示，1)、对照组和腺瘤患者的肠道微生物群组成不同，2)1个细菌属（Slackia）与对照组显著相关，4个细菌属（放线菌属、托托菌属、梭菌属和嗜血杆菌属）与腺瘤内癌组显著相关，3)多个细菌种与每种类型显著相关(对照组：coprostanoligens真杆菌；腺瘤癌：溶牙放线菌、脆弱拟杆菌、耐索梭菌；各种梭杆菌、副流感嗜血杆菌、体核普雷沃氏菌、戈多氏链球菌和异细孔菌)。在日本人群中，肠道微生物特性在对照组和腺内癌患者之间存在差异，表明肠道微生物群与结直肠癌的预防和发展有关。
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in Japan. The etiology of CRC has been linked to numerous factors including genetic mutation, diet, life style, inflammation, and recently, the gut microbiota. However, CRC-associated gut microbiota is still largely unexamined. This study used terminal restriction fragment length polymorphism (T-RFLP) and next-generation sequencing (NGS) to analyze and compare gut microbiota of Japanese control subjects and Japanese patients with carcinoma in adenoma. Stool samples were collected from 49 control subjects, 50 patients with colon adenoma, and 9 patients with colorectal cancer (3/9 with invasive cancer and 6/9 with carcinoma in adenoma) immediately before colonoscopy; DNA was extracted from each stool sample. Based on T-RFLP analysis, 12 subjects (six control and six carcinoma in adenoma subjects) were selected; their samples were used for NGS and species-level analysis. T-RFLP analysis showed no significant differences in bacterial population between control, adenoma and cancer groups. However, NGS revealed that i), control and carcinoma in adenoma subjects had different gut microbiota compositions, ii), one bacterial genus (Slackia) was significantly associated with the control group and four bacterial genera (Actinomyces, Atopobium, Fusobacterium, and Haemophilus) were significantly associated with the carcinoma-in-adenoma group, and iii), several bacterial species were significantly associated with each type (control: Eubacterium coprostanoligens; carcinoma in adenoma: Actinomyces odontolyticus, Bacteroides fragiles, Clostridium nexile; Fusobacterium varium, Haemophilus paraiufluenzae, Prevotella stercorea, Streptococcus gordonii, and Veillonella dispar). Gut microbial properties differ between control subjects and carcinoma-in-adenoma patients in this Japanese population, suggesting that gut microbiota is related to CRC prevention and development.