title: 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.
abstract: 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 parainfluenzae, 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.
authors.affiliation: Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Kasai
authors.affiliation: Department of Molecular and Laboratory Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Moritani
authors.affiliation: Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Oya
authors.affiliation: Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Molecular and Laboratory Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tameda
authors.affiliation: Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Shiraki
authors.affiliation: Department of Cardiology and Nephrology, Tsu, Mie, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takei
authors.affiliation: Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Mie 510-8561, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Takase
mesh_terms: D000236:Adenoma / Q000382:microbiology*; D000328:Adult; D001419:Bacteria / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D015179:Colorectal Neoplasms / Q000382:microbiology*; D004275:DNA, Ribosomal / Q000235:genetics; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D064368:Healthy Volunteers; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S