基于双生子出生队列的肠道菌群多样性与婴儿肥胖的关联研究

Childhood obesity is a serious problem with complex causes. Researches shown that the diversity disorder of gut microbiome is an important cause of adult and elder children obesity, however its association with infants’ obesity is still in the air. .Based on the Wuhan Twin Birth Cohort Study, we use the nested case-control study design, and select 120 twins with the ones overweight/obesity at 12-month-old as case group and their compatriots who were at normal weight from birth, 1st, 6th to 12th month-old as controls. The Misq platform is used to complete the 16S rDNA sequencing procedure. The bioinformatics analysis softwares like R and Lefse, and biostatistics analysis tools such as nonparametric test and conditional logistic regression analysis are introduced to compare the diversity of gut microbiome between cases sand controls, in order to find out the candidate overweight/obesity high-risk microbiota. At the same time, the linear mixed effect model is established to analyze the associations between the candidate high-risk gut microbiota and infants’ BMIs at multiple time points, so as to evaluate the influence of gut microbiota diversity on BMI dynamics and finally to verify the hypothesis that gut microbiota diversity is a risk factor for infants’ overweight/obesity. .It is expected that the results of the study will help further elucidating the pathogenesis of childhood obesity, and provide scientific grounds for formulating the strategy of early prevention.

儿童肥胖问题日益严重，与诸多因素有关。研究发现肠道菌群多样性与成人及大龄儿童肥胖关系密切，但其与婴儿肥胖的关联尚不明确。.本研究基于武汉双生子出生队列研究平台，采用巢式病例对照研究方法，以120对双生子中12月龄超重/肥胖的个体为病例，以其从出生、1、6到12月龄体重均正常的同胞为对照，利用Misq高通量测序平台完成各月龄粪便16S rDNA测序，通过R和Lefse等生物信息分析软件，采用非参数检验和条件logistics回归分析等方法，比较两组婴儿菌群多样性差异，寻找超重/肥胖的候选高危菌群；同时建立混合线性模型，分析候选高危菌群多样性与婴儿多时点BMI的关联，评估菌群多样性对BMI动态变化的影响，验证“肠道菌群多样性是婴儿超重/肥胖的影响因素”的假设。.研究结果将有助于进一步阐明儿童早期肥胖的成因，为制定早期干预策略提供科学依据。

儿童肥胖问题日益严重，与诸多因素有关。研究发现肠道菌群多样性紊乱与成人肥胖关系密切，但其与婴儿肥胖的关联尚不明确。.本研究基于武汉双生子出生队列研究平台，本项目开展双生子6月龄、12月龄和24月龄粪便标本细菌16S rDNA检测，分阶段先后开展6月龄小样本巢式病例对照研究、12月龄病例对照研究和大样本纵向数据分析。.综合本研究各阶段研究结果，主要发现如下：随着年龄增长双生子菌群丰度和多样性均有上升，个体间异质性先随着年龄增长不断增大后不断减少；梭状芽胞杆菌在6月龄超重/肥胖儿童中丰度更高；副拟杆菌在儿童6月龄至24月龄发育过程中变化轨迹与其BMI_Z有显著关联。.本研究结果一方面在双生子中论证了儿童早期菌群发展的主要规律，另一方面发现了可能与儿童早期肥胖或体格发育密切相关的菌属梭状芽胞杆菌和副拟杆菌。本研究结果为进一步开展儿童肥胖早期成因研究提供的数据支持，未来将进一步探讨本项目主要发现的作用机制。