肠道微生物的代谢及生理功能研究
人体内寄居的微生物的种类、结构及其功能陆续被揭示。其中，占比最大且对人类健康影响最广泛的是肠道微生物。迄今为止，肠道内已鉴定了50多种细菌门，而人类肠道中只有2种占主导地位：拟杆菌门和厚壁菌门。人类肠道微生物的结构组成因人而异，主要受母亲菌群、基因背景、饮食习惯、生活环境及药物使用等因素影响。基于基因测序、无菌动物及其他细菌研究手段，肠道微生物的代谢和生理功能已被部分揭示，主要包括：1）代谢药物成分；2）参与维生素及氨基酸代谢；3）训练及激活免疫系统；4）促进血管生成；5）参与脂肪代谢及储存；6）调控骨密度；7）保护肠屏障及血脑屏障；8）抵御病原菌及病毒感染；9）参与中枢及外周神经系统的成熟及调控；10）食物消化及发酵。这些肠道微生物驱动的代谢及生理功能的重要性也表明其在人类生理、病理过程中扮演重要角色。然而，肠道微生物仍然存在许多未解之谜，这也是本中心在该方向的主要研究目标。
肠道微生物影响消化道生理病理研究
肠道菌群对宿主个体的生理自稳起着非常重要的作用，当肠道菌群失调时，机体会发生一系列生理病理改变。肠道菌群可通过影响消化道黏膜屏障功能、通过它们表达的成分和代谢产物及调节机体免疫功能等机制来影响机体的生理活动，其影响范围可达全身多个系统，包括消化系统、内分泌系统、循环系统甚至神经系统等。肠道菌群对宿主消化系统生理结构和功能影响是多方面，并且对于肠道菌群变化与疾病发生发展的因果关系及作用机制还是知之甚少。该方向主要聚焦于肠道菌群与消化道正常黏膜发育以及常见疾病之间的相互关系以及挖掘宿主-微生物交互的内在机制，为消化道相关疾病诊断提供新的标记物。
肠道微生物介导中医药治疗的机制研究
以肠道菌群为靶向的治疗已成为一种很有前景的防病治病策略，越来越多的研究表明中医药在治疗许多疾病方面所发挥的作用是通过肠道微生物介导的。生物大数据研究的推进也为中医药研究和肠道菌群研究提供了更全面的视角。中药成分可调控肠道微生物结构及代谢功能，还可通过影响肠道微生态，调控宿主生理功能。同时，肠道微生物也参与中药的代谢，中药的药理活性依赖于肠道微生物群的转化，以提高中药的生物利用度。由于肠道菌群的多样性及复杂性，中医药的多成分及多靶点性，肠道微生物介导中医药治疗的具体机制尚需进一步探索。该方向研究的主要目标基于肠道微生物阐明中药发挥药效作用的物质基础及分子机制，为以肠道菌群为靶点的中医药治疗提供依据。
Metabolism and physiological function of gut microbes
Human body is colonized by a huge amount of microorganisms mostly located in the gastrointestinal tract. To date, more than 50 bacterial phylums have been identified in the human gut, with two dominant phylums: Bacteroidetes and Firmicutes. The structure of human intestinal microbes is mainly affected by maternal flora, genetic background, eating habits, living environment and drug use. Based on gene sequencing, germ-free animals and other bacterial research methods, the metabolism and physiological functions of gut microbes have been partially revealed, including: 1) Drug metabolism; 2) Participate in vitamin and amino acid metabolism ; 3) Activate and reshape the immune system; 4) Promote angiogenesis; 5) Participate in lipid metabolism and storage; 6) Regulate bone density; 7) Protect intestinal epithelia barrier and blood-brain barrier; 8) Protect from pathogens and virus infection; 9) Involve in maturation and regulation of central and peripheral nervous systems; 10) Food digestion and fermentation. However, there are still many unsolved questions in gut microbes, which are the main research areas of this direction.
Effects of intestinal microbe on gut physiology and pathology
Intestinal flora plays an important role in the physiological stability of the host. Growing data suggests a causal role of a dysbiotic microbiota in several pathologies, including the digestive system, endocrine system, circulatory system and even nervous system. The intestinal flora may affect the physiological structure and function of the host digestive system in many aspects, and the causal relationship and mechanism between intestinal flora and the occurrence and development of diseases are still poorly understood. This direction is focused on the relationship between intestinal flora and the fundamental biological processes that drive common diseases, so as to provide new markers for the diagnosis of gut-related diseases.
Mechanism of intestinal microbiome mediated TCM therapy
Microbiota-targeted therapy has become a promising strategy for disease prevention and treatment. Advances in systems biology, particularly based on the omics approaches, have resulted in a paradigm shift in both traditional Chinese medicine (TCM) and the gut microbiome research. Studies have proven that TCM could be used as a perfect agent to treat many kinds of diseases, many of which were mediated by gut microbiome. Biological big data research also provides a more comprehensive perspective for the study of TCM and intestinal flora. Due to the diversity and complexity of intestinal flora, the multi-component and multi-target nature of TCM, the potential of TCM studies at the molecular level remains to be better exploited. The main research area of this direction is to analyze the “TCM-host-gut microbiome” interaction network from a holistic perspective, and thus to provide a gut-microbiome-targeted basis for TCM therapy.