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

描述(申请人提供)：结直肠癌起源于结肠镜检查可识别的腺瘤和锯齿状结肠息肉。一些研究已经报道了粪便或结肠粘膜中的微生物区系组成与结直肠癌之间的关系。这些研究通常规模较小，没有对宿主基因型或儿童早期暴露进行控制，这两个因素是设定肠道微生物区系的最大影响因素。我们建议通过比较45对与结肠息肉病史不一致的同卵双生子(MZ)的微生物区系多样性和分类群来确定肠道微生物区系和结肠息肉之间的关联。使用息肉不协调的MZ双胞胎作为受试者是一种优势，因为儿童早期的环境和遗传因素都是受控制的。从加州双胞胎计划招募的双胞胎将收集并返回标本试管中的粪便样本，我们提供的样本还包括饮食问卷、生活方式和暴露问卷、签署的HIPAA表格，以允许收集核实息肉和结肠镜检查的医疗记录，以及通过邮寄签署的知情同意书。基于之前对淋巴瘤不协调双胞胎中微生物区系的研究，我们预计遵从率为70%。在马里兰大学基因组科学研究所的国际微生物组专家雅克·拉维尔博士的实验室里，将使用16RS对150毫克的粪便进行测序，以确定微生物区系的多样性和分类群。拉威尔博士的团队将执行DNA测序分析和生物信息学，并提供微生物区系的多样性衡量标准(香农指数衡量人内差异或阿尔法多样性，Unifrac衡量人与人之间的差异，或贝塔多样性)。将使用QIIME和其他标准软件对物种进行分类。我们将使用条件Logistic回归框架来研究患有和不伴有结肠息肉的MZ双胞胎在肠道微生物群多样性和特定细菌种类方面的差异。每增加1个单位(即生物标记物增加1个标准差)的最小可检测优势比为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区系差异相似(平均差异外推为OR)。这项先导性研究的意义在于有可能证明肠道微生物区系和结肠息肉之间的关系不受宿主基因或儿童早期暴露的影响。

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.