PNAS：人类元基因组研究期待“中国劲舞”
优势之一：样本完整
当前，我国正在经历从营养不良到营养过剩的饮食结构转变，人体微生物群落结构相应发生变化，这在不同经济发展地区都有很好的样本，加之我国人口众多，不同民族、地区、生活习惯和疾病类型都会形成丰富多样的人体菌群结构，蕴涵十分丰富的基因资源。赵立平教授表示，“发达国家和地区已经经历完了饮食结构的改变，再想找到这样的样本很困难。”因此，我们更应加紧开展相关研究，弄清不同饮食结构和菌群变化对糖尿病、肥胖、癌症等重大疾病的影响，从而采取相应措施阻断或逆转慢性病增加的趋势。
优势之二：中医药
改变一个人的基因是困难的，而改变生活在人体内的微生物组成是相对容易国的传统医学有许多药物、疗法很可能是通过改变肠道菌群的结构、影响肠道的代谢来完成治疗作用的。因此，中医中药在人类元基因组研究中可能会扮演重要角色。赵立平教授认为，我们应把中药里一些能干预肠道菌群、调节人体健康、防治慢性病的优秀遗产，采用人类元基因组学、代谢组学、计算生物学等研究方法进行挖掘、整理，去粗取精、去伪存真，让国际社会能理解和认可这些药物和疗法的效果,这也是对国际医学发展的一个重要贡献。
优势之三：多学科团队
研究人类元基因组，不仅仅是一个基因测序的问题，更需要微生物学、人体生理学、生物信息学、计算机科学等多学科的联合攻关，来进行其功能研究，是一场场高难度的“集体舞”。在过去几年里，我国科学家以共同感兴趣的项目为纽带，形成了一支多学科交叉的研究团队，并与国外一流的研究机构建立了很好的合作关系，使得我国元基因组研究形成了“测序与功能并重，基础与临床同步”的重要特色，在国际人类元基因组研究中独树一帜。赵立平教授强调，这次发表在PNAS上的研究成果就充分展示了多学科交叉研究的威力：来自我国上海交通大学系统生物医学研究院、浙江大学第一附属医院、国家人类基因组南方研究中心和中科院武汉物理与数学研究所和英国帝国理工大学5个机构组成的多学科交叉研究国际团队，经过近3年的联合攻关，通过对一个四世同堂的中国家庭7位成员的肠道微生物组成和人体代谢特征进行详细分析，初步鉴定出肠道内参与人体代谢过程的一些重要的功能细菌，为深入理解菌群参与人体健康的机理奠定了很好的基础，也为功能元基因组学提供了很好的方法。
赵立平教授强调，正如中医所说的“上工治未病”，当前对疾病的预防和早期干预比治疗更加重要。通过早期发现微生物群落的变化来预测和预警疾病的发生；在疾病的早期发病阶段，通过纠正菌群的失衡加以干预，成本低且效果明显。因此，我国应积极发挥自身的独特优势，在人类元基因组研究的国际竞争中占据制高点，为促进人类健康做出重要贡献。（中国医药报）
生物谷推荐原始出处：
Published online on February 5, 2008, 10.1073/pnas.0712038105
PNAS | February 12, 2008 | vol. 105 | no. 6 | 2117-2122
BIOLOGICAL SCIENCES / MICROBIOLOGY
Symbiotic gut microbes modulate human metabolic phenotypes
Min Li*, Baohong Wang
, Menghui Zhang*, Mattias Rantalainen
, Shengyue Wang
, Haokui Zhou*, Yan Zhang*, Jian Shen*, Xiaoyan Pang*, Meiling Zhang*, Hua Wei*, Yu Chen, Haifeng Lu, Jian Zuo, Mingming Su*, Yunping Qiu*, Wei Jia*, Chaoni Xiao¶,||, Leon M. Smith, Shengli Yang*, Elaine Holmes, Huiru Tang¶,**, Guoping Zhao,**, Jeremy K. Nicholson,**, Lanjuan Li,**, and Liping Zhao*,**
*Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine at Shanghai Jiao Tong University, Shanghai 200240, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China; ¶State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China; ||Graduate University of the Chinese Academy of Sciences, Beijing 100049, China; Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center, Shanghai 201203, China; and Department of Biomolecular Medicine, Faculty of Medicine, Imperial College London, South Kensington SW7 2AZ, United Kingdom
Communicated by Zhu Chen, Shanghai Second Medical University, Shanghai, People's Republic of China, December 22, 2007 (received for review October 27, 2007)
Humans have evolved intimate symbiotic relationships with a consortium of gut microbes (microbiome) and individual variations in the microbiome influence host health, may be implicated in disease etiology, and affect drug metabolism, toxicity, and efficacy. However, the molecular basis of these microbe–host interactions and the roles of individual bacterial species are obscure. We now demonstrate a"transgenomic" approach to link gut microbiome and metabolic phenotype (metabotype) variation. We have used a combination of spectroscopic, microbiomic, and multivariate statistical tools to analyze fecal and urinary samples from seven Chinese individuals (sampled twice) and to model the microbial–host metabolic connectivities. At the species level, we found structural differences in the Chinese family gut microbiomes and those reported for American volunteers, which is consistent with population microbial cometabolic differences reported in epidemiological studies. We also introduce the concept of functional metagenomics, defined as "the characterization of key functional members of the microbiome that most influence host metabolism and hence health." For example, Faecalibacterium prausnitzii population variation is associated with modulation of eight urinary metabolites of diverse structure, indicating that this species is a highly functionally active member of the microbiome, influencing numerous host pathways. Other species were identified showing different and varied metabolic interactions. Our approach for understanding the dynamic basis of host–microbiome symbiosis provides a foundation for the development of functional metagenomics as a probe of systemic effects of drugs and diet that are of relevance to personal and public health care solutions.
covariation analysis | gut microbiota | metabonomics | metabotype | metagenomics
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