基于宏基因组学探讨湿热体质湿重于热与热重于湿的发生机制

Damp-heat constitution is one of the most common unbalanced constitutions of Traditional Chinese Medicine (TCM), accounted for 9.08% of the general population in China. However, we still know very little about the mechanism of damp-heat constitution. On the basis of damp heat, damp-heat constitution can be divided into damp-heat constitution with predominant damp and with predominant heat. Our previous research showed that damp-heat constitution was closely related to gut microbiota. The mechanism of damp-heat constitution with predominant damp and with predominant heat are still unclear. Based on our preliminary studies, we research the different gut microbiota and tongue coating microbiota through metagenomics among damp-heat constitution with predominant damp, with predominant heat and balanced constitution. First, we explore the role of gut microbiota in the mechanism of damp-heat constitution with predominant damp and with predominant heat. Then, we research how tongue coating microbiota affect the tongue coating of damp-heat constitution with predominant damp and with predominant heat. Finnaly, we also reveal how Huopu Xialing decoction and Baihu Jia Cangzhu decoction intervene damp-heat constitution with predominant damp and with predominant heat, respectively. This will not only provide objective evidence for the standardization of constitution of TCM and for the integrity and complicacy of the Chinese medicine treatment, but also build the bridge between traditional tongue diagnosis and molecular systems biology, and promote the development of the preventive treatment of TCM.

湿热体质为最常见的偏颇体质之一，占中国一般人群的9.08%，然而目前对它的发生机制知之甚少。根据湿、热之偏重，湿热体质可分为湿重于热与热重于湿，前期研究发现湿热体质的发生与肠道微生物密切相关，而湿热体质湿重于热、热重于湿的发生机制仍不清楚。本项目拟在前期研究的基础上，以湿热体质湿重于热、热重于湿和平和体质人群为研究对象，利用宏基因组学技术，研究肠道菌群在湿热体质人群湿重于热、热重于湿发生中的作用机制，探寻舌苔菌群对湿热体质湿热偏重舌苔的影响，并揭示中药复方藿朴夏苓汤、白虎加苍术汤对湿热体质湿重于热、热重于湿干预的作用机制。这不仅将为中医体质辨识标准化、客观化提供证据，为中药复方治疗作用的整体性、复杂性及多靶点性提供新的理论依据，也将为传统舌诊与分子系统生物学之间架起桥梁，还将促进中医治未病的发展。

湿热体质是以湿热内蕴为主要特征的一种体质类型，根据湿、热之偏重，湿热体质可分为湿重于热与热重于湿。中医药在防治湿热体质方面积累了丰富的经验，藿朴夏苓汤、白虎加苍术汤分别是治疗湿热体质湿重于热、热重于湿的有效方剂。主要研究内容及方法：1、本项目采用16SrDNA检测并分析湿热体质湿重于热、热重于湿的肠道菌群特征；2、分别采用藿朴夏苓汤、白虎加苍术汤对湿热体湿重于热、热重于湿进行干预，分析干预前后肠道菌群变化。重要结果及关键数据：本项目研究表明湿热体质湿重于热组与热重于湿组菌群结构存在差异，热重于湿组肠道菌群较湿重于热组更丰富。湿重于热组的优势菌门为Proteobacteria，优势菌属为Bacteroides、Parabacteroides和Phascolarctobacterium。热重于湿组的优势菌门为Bacteroidetes，优势菌属为Prevotella。湿热体质人群Proteobacteria及Bacteroides丰度升高可能是其湿重于热的发生机制，而Bacteroidetes和Prevotella丰度升高可能是其热重于湿的发生机制。湿热体质湿重于热组经藿朴夏苓汤干预后，其菌群丰度升高、结构改变，α多样性和β多样性均趋向于平和体质。藿朴夏苓汤能显著增加Firmicutes、Faecallbacterium丰度，降低Bacteroidetes、Bacteroides丰度显著降低，门的丰度恢复到与平和体质一致，属水平的丰度趋向于平和体质水平。湿热体质热重于湿组经白虎加苍术汤干预后，其菌群丰度升高、结构改变，α多样性与平和体质一致，β多样性趋向于平和体质。白虎加苍术汤能显著增加热重于湿组Firmicutes、Proteobacteria丰度，降低Bacteroidetes、Prevotella、Blautia、Actinobacillus丰度，门和属的菌种丰度趋向于平和体质。科学意义：明确湿热体质湿热偏重肠道菌群分布特征及湿热偏重的发生机制，对湿热偏重的特异表现与动态把握可以更准确地指导临床用药、提高疗效。同时也为中药复方治疗作用的整体性、复杂性及多靶点性提供新的理论依据，对防治疾病、促进健康具有重要意义，也是中医治未病思想的体现。