Comparison of the Fecal Microbiome in Identical Twins Discordant for Colon Polyps

结肠息肉不一致的同卵双胞胎粪便微生物组的比较

• 批准号: 8639320
• 负责人: Wendy Cozen
• 金额: $ 8.21万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8639320
• 关键词: Age; Bacteria; Bacterial DNA; Bioinformatics; Biological Assay; Biological Markers; California; Cessation of life; Classification; Collection; Colon; Colonic Polyps; Colonoscopy; Colorectal Cancer; Computer software; Cross-Sectional Studies; DNA Sequence; Development; Diagnosis; Diet; Environment; Feces; Genetic; Genome; Genotype; Health Insurance Portability and Accountability Act; Immunity; Influentials; Informed Consent; Institutes; International; Intervention; Laboratories; Lead; Life; Life Style; Logistic Regressions; Lymphoma; Mails; Malignant Neoplasms; Maryland; Measures; Medical Records; Monozygotic Twinning; Monozygotic twins; Mucous Membrane; Odds Ratio; Persons; Pilot Projects; Play; Polyps; Population; Prevention; Probiotics; Public Health; Questionnaires; Recording of previous events; Recruitment Activity; Reporting; Risk; Role; Sampling; Science; Specimen; Staging; Stratification; Taxon; Tube; Twin Multiple Birth; Universities; base; early childhood; gut microbiota; indexing; member; microbial community; microbiome; programs; public health relevance; pyrosequencing

DESCRIPTION (provided by applicant): CRC arises from adenomatous and serrated colon polyps that are identifiable with colonoscopy. Several studies have reported an association between microbiota composition in feces or colonic mucosa, and CRC. These studies were generally small and did not control for host genotype or early childhood exposures, the two most influential factors in setting the gut microbiota. We propose to determine the association between the gut microbiota and colon polyps by comparing microbiota diversity and taxa in 45 monozygotic (MZ) twin pairs discordant for a history of colon polyps. Using polyp-discordant MZ twins as subjects is an advantage because both early childhood environment and genetic factors are controlled. Twins recruited from the California Twin Program will collect and return stool samples in specimen tubes that we provide, along with a diet questionnaire, lifestyle and exposure questionnaire, a signed HIPAA form to allow collection of medical records verifying the polyps and colonoscopy, and a signed informed consent, by mail. Based on a previous study of microbiota in lymphoma-discordant twins, we expect a 70% compliance rate. Microbiota diversity and taxa will be determined using 16rs sequencing of 150 mg of stool in the laboratory of Dr. Jacques Ravel, an international microbiome expert at the University of Maryland's Institute for Genome Sciences. Dr. Ravel's team will perform the DNA sequencing assays and bioinformatics and provide microbiota measures of diversity (Shannon's index as a measure of within person differences or alpha diversity, and Unifrac to measure between-person differences, or beta diversity). Taxonomic classification to the species level will be performed using QIIME and other standard software. We will use a conditional logistic regression framework to investigate the difference in gut microbiome diversity and specific bacterial species between MZ twins with and without colon polyps. The minimum detectable odds ratio for a 1 unit increase (i.e. a 1 SD increase in the biomarker) is 1.86 (¿ = 0.05) and 2.48 (¿ = 0.002), which is similar to the microbiota differences observed in our pilot study of 13 lymphoma-discordant pairs (mean differences extrapolated to an OR). The significance of this pilot study lies in the potential to demonstrate a relationship between the gut microbiota and colon polyps independent of host genotype or early childhood exposures.

描述（由应用程序提供）：CRC来自可鉴定出结肠镜检查的腺瘤和序列结肠息肉。几项研究报道了粪便或结肠粘膜中的微生物群组成与CRC之间的关联。这些研究通常很小，无法控制宿主基因型或幼儿暴露，这是设定肠道微生物群的两个最具影响力的因素。我们建议通过比较45个单卵（MZ）双子对中的微生物群多样性和分类群来确定肠道微生物群和结肠息肉之间的关联。使用息肉差异MZ双胞胎作为受试者是一个优势，因为幼儿环境和遗传因素都得到控制。从加利福尼亚双胞胎计划中招募的双胞胎将收集和退回样品管中的粪便样品，以及我们提供的饮食问卷，生活方式和曝光问卷调查表，签名的HIPAA表格，允许收集医疗记录，以验证息肉和结肠镜检查，并通过邮件收集签名。基于先前对淋巴瘤双胞胎微生物群的研究，我们预计合规率为70％。 Microbiota多样性和分类单元将使用16RS测序在马里兰大学基因组科学研究所的国际微生物组专家Jacques Ravel博士的实验室中进行16RS测序。 Ravel博士的团队将执行DNA测序测定法和生物信息学，并提供多样性的微生物群测量（Shannon的指数是对人内部差异或Alpha多样性的衡量，以及衡量人之间差异或Beta多样性的单irifrac）。分类学分类将使用QIIME和其他标准软件进行。我们将使用条件逻辑回归框架来研究肠道微生物组多样性和具有结肠息肉和没有结肠息肉的MZ双胞胎之间的特定细菌物种的差异。 1单位增加（即生物标志物增加1 SD）的最小可检测优势比为1.86（= 0.05）和2.48（= 0.002），这与我们的13个淋巴瘤 - 诊断差异（平均值差异）的飞行员研究中观察到的微生物群差异相似。这项试验研究的意义在于可能证明肠道菌群与肠息肉与宿主基因型或幼儿暴露无关的结肠息肉之间的关系。