基于移民队列、肠道菌群及代谢组学研究藏族牧民中膳食模式改变对代谢健康的作用

我国地区民族间健康及生活方式差异大。藏族牧民从牧区向城镇移民中肥胖、代谢紊乱高发，膳食改变是重要原因。申请人横断面研究发现，以精米白面等为特征的城镇膳食模式和牧民肥胖、代谢综合征相关；以肉奶类为特征的牧区膳食无相关。由此提出科学假说：藏族牧民向城镇移民中膳食改变引起肥胖和代谢异常；肠道菌群及衍生代谢物组成和功能改变介导此关系。本项目基于申请人基线研究：1）开展队列研究，追访原有1003名藏族牧民，进行调查及生化检测。应用因子分析、混合效应模型等研究膳食模式改变及影响因素，膳食改变是否影响代谢健康。2）对其中90名牧民及新增30名汉族居民开展肠道菌群和衍生代谢物子研究。应用16S rDNA测序、宏基因组测序和代谢组学，从长时、短时膳食改变两个时间维度，从菌种、基因、代谢、功能多个维度探索介导膳食和代谢健康关系的机制。为制定特殊人群膳食指导及健康促进提供依据，为代谢异常防治提供潜在靶点。

Large variations exist in health status and lifestyle among ethinic groups and geographic areas. Tibetan pastoralists had high prevalence of obesity and metabolic disorders in the process of migrating from pastoral to urban areas. The dietary transition may be one of the key reasons. Our previous study showed the urban dietary pattern – characterized by refined carbohydrates, etc.—was associated with obesity and metabolic syndrom among Tibetan pastoralists; by contrast, no association was found for the traditional pastoral diet characterized by beef, mutton, dairy products, etc. Hence we raise the reserch hypothesis: the dietary transition in pastoral-to-urban migration among Tibetan pastoralists causes increased obesity and metabolic disorders; the gut microbiome and its metabolites mediate the relationship between dietary transition and metabolic health. This project is a cohort study built on our previous baseline survey. The 1003 Tibetan pastoralists in the baseline will be followed up once. Questionnaires, dietary assessment, anthropometric measurements and biomarker tests for metabolic health will be conducted. Principle component analysis, Kapper consistency test, and mixed-effect model will be employed (1) to describe the dietary pattern change and analyze the influencing factors, and (2) to explore the impact of dietary change to metabolic health among Tibetan pastoralists. A sub-study invloving 90 Tibetan pastoralists and 30 Han urban residents will also be conducted using the gut microbilomics and metabolomics techniques, to explore the mechanisms of the short- and long-term impacts of dietary change to the metabolic health from multiple aspects including gut bacteria genus, gene, metabolism and function, etc. This study will provide evidence to guide population-specific dietary recommendations and health promotion activities, meanwhle to provide potential targets for preventing and treating metabolic disorders.