中国人群肠道微生物鸟枪法宏基因组测序研究进展

Shotgun metagenome sequencing of Chinese gut microbiota: a review

摘要:

肠道微生物与人类健康的相关性研究仍然是当前生命科学研究领域的前沿热点之一。不依赖培养的 16S rRNA基因高通量测序是当前的主要研究手段。但随着测序成本的降低和数据分析方法的日渐成熟，宏基因组鸟枪法测序因具有信息量更大、更全等优势，将逐渐成为今后一段时间内研究肠道微生物组的重要手段。美国在人类微生物组计划的资助下，对30 805份样品进行了肠道微生物宏基因测序分析。通过NCBI PubMed和SRA数据库检索，共发现72项研究收集了约10 000份中国人的肠道样品用于宏基因组测序。但到目前为止，仅56项研究进行了公开发表，其中与代谢性疾病相关的文献16篇，与感染和免疫性疾病相关的文献16篇，与心脑血管疾病相关的文献12篇。由于采样地点以北京、广州、上海等大城市为主，测序平台和测序分析方法均存在较大差异，且大部分研究仍以相关性分析为主，相关研究成果在临床疾病诊疗中所发挥的作用仍非常有限。规范采样方法、标准化测序平台和数据分析流程，开展多中心平行研究将有助于数据整合和比较分析。同时，结合使用转录组、蛋白质组和培养组学等多组学方法开展功能验证和分子作用机制研究，将有利于更好地将肠道微生物研究成果服务于临床疾病诊疗。

Abstract:

The research on the relationship between gut microbiota and human health continues to be a hot topic in the field of life science. Culture independent 16S rRNA gene high-throughput sequencing is the current main research method. However, with the reduction of sequencing cost and the maturity of data analysis methods, shotgun metagenome sequencing is gradually becoming an important method for the study of gut microbiome due to its advantages of obtaining more information. With the support from the human microbiome project, 30 805 metagenome samples were sequenced in the United States. By searching NCBI PubMed and SRA databases, it was found that 72 studies collecting about 10 000 Chinese intestinal samples were used for metagenome sequencing. To date, only 56 studies were published, including 16 related to metabolic diseases, 16 related to infectious and immune diseases, and 12 related to cardiovascular and cerebrovascular diseases. The samples were mainly collected in Beijing, Guangzhou, Shanghai and other cosmopolitan cities, where great differences exist in sequencing platforms and methods. The outcome of most studies are based on correlation analysis, which has little practical value in guiding the diagnosis and treatment of clinical diseases. Standardizing sampling methods, sequencing platform and data analysis process, and carrying out multi center parallel research will contribute to data integration and comparative analysis. Moreover, insights into the functional verification and molecular mechanism by using the combination of transcriptomics, proteomics and culturomics will enable the gut microbiota research to better serve the clinical diagnosis and treatment.