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

描述（由申请人提供）：结直肠癌起源于结肠镜检查可识别的腺瘤状和锯齿状结肠息肉。一些研究报道了粪便或结肠粘膜微生物群组成与结直肠癌之间的关系。这些研究通常规模较小，并且没有控制宿主基因型或儿童早期暴露，这是设置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对结肠息肉病史不一致的同卵双胞胎的微生物群多样性和分类群来确定肠道微生物群与结肠息肉之间的关系。使用息肉不一致的MZ双胞胎作为研究对象具有优势，因为早期儿童环境和遗传因素都是可控的。从加州双胞胎项目中招募的双胞胎将收集并送回我们提供的标本管中的粪便样本，同时提供饮食问卷，生活方式和暴露问卷，签署的HIPAA表格，允许收集验证息肉和结肠镜检查的医疗记录，以及通过邮件签署的知情同意书。根据先前对淋巴瘤不一致双胞胎微生物群的研究，我们预计70%的依从率。微生物群的多样性和分类群将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博士的实验室中使用150毫克粪便的16rs测序来确定。拉威尔博士的团队将进行DNA测序分析和生物信息学，并提供微生物群多样性的测量方法（香农指数是衡量人内部差异或α多样性的指标，而Unifrac指数是衡量人之间差异或β多样性的指标）。采用QIIME等标准软件进行种级分类。我们将使用条件逻辑回归框架来研究患有和不患有结肠息肉的MZ双胞胎之间肠道微生物群多样性和特定细菌种类的差异。每增加1个单位（即生物标志物增加1个标准差），可检测到的最小优势比分别为1.86（¿= 0.05）和2.48（¿= 0.002），这与我们在13对淋巴瘤不一致对的初步研究中观察到的微生物群差异相似（平均差异外推为OR）。这项初步研究的意义在于有可能证明肠道微生物群与结肠息肉之间的关系独立于宿主基因型或儿童早期暴露。

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.