肠道微生物菌群与宿主的健康和疾病密切相关，而且肠道微生物来源的天然产物在这一关系中发挥重要作用，因此，肠道微生物菌群不仅是药物治疗的潜在新靶点，而且也是药物发现的重要来源。不同生活环境的动物肠道微生物菌群多样性及生物功能也有所差异，特殊生境可能导致动物肠道菌群基因资源和功能更加特异。牦牛是青藏高原特产动物，恶劣的高寒环境对牦牛肠道微生物菌群的影响及其来源的天然产物相关研究尚未见报道。本项目拟以青藏高原全放牧牦牛的新鲜粪便为研究材料，通过非依赖培养的16S rRNA基因高通量测序及宏基因组测序方法，肠道可培养微生物分离和属种鉴定，抗菌抗肿瘤活性筛选、活性分子及其生物合成基因簇的挖掘，最终揭示青藏高原牦牛的肠道微生物多样性、功能及其来源的活性天然产物。本项目的顺利实施，将为解析青藏高原牦牛对高寒环境的生态适应性提供新的思路，对该地区牦牛产业及扩大特殊微生物药物来源具有重要意义。

Gut microbiota (GM) is closely related with host health and disease, in which GM-generated natural products (NPs) play an important role as mediators. Therefore, GM is not only a new potential target for medical therapy, but also a key source for new drug discovery. The biodiversity and biological functions of animal GM living in different environments are also distinctive，reasoning that the special habitats undoubtedly induce the gene resources and functions of animal GM to be more unique. The yak (Bos grunniens), a characteristic animal dwelling in the Qinghai-Tibet Plateau (QTP), of which the investigations on the effects of harsh alpine environment on the GM and derived NPs have not been reported previously. The project will intend to use the fresh feces of the grazing yaks living in the QTP as the material, systematically revealing the GM diversity, biological functions and GM-generated bioactive natural products from the yaks in the QTP, via the combination of the culture-independent 16S rRNA high-throughput sequencing and metagenomic sequencing, the isolation and identification of culture-dependent GM mirobes, the screening of antibacterial activity, the mining of active molecules and their biosynthetic gene clusters. The successful implementation of the project will shed light on deciphering the mechanistic details of the ecological adaptability of the yak in a new perspective, which is also of great significance for the local yak industry and expanding the microbial drug source.