Sep. 26, 2012 BGI announces the online publication in the journal Nature of a novel metagenomic study on human gut microbiota and their potential impact on type 2 diabetes (T2D), the most common form of diabetes. This work lays an important foundation for comprehensively understanding the genetic characteristics of gut microbiota and their relationship to T2D risk, as well as providing a new way of classifying microbes detected by DNA sequence. The work here also opens the way for transferring the potential value of a gut-microbiota-based approach into a means for clinical assessment and diagnosis of patients at risk of this disease.
T2D is a major chronic disease of modern societies and threatens the health of populations throughout the world. The continual and rapid increase in the prevalence of T2D has created a race against time for researchers worldwide to find new approaches to diagnose and treat the disease. T2D is a heterogeneous and multifactorial disease, influenced by a number of different genetic and environmental factors. While there are treatments to modulate its impact available, there remains great need to improve these therapies, and the disease cannot be cured.
Considering the important impact of gut microbiota on human diseases, such as T2D, BGI in collaboration with other institutes has focused on mining the gut microbiota information with the aim of fully understanding their molecular characteristics and using this to benefit human health. In this study, using deep next-generation shotgun sequencing, they developed a protocol for carrying out a metagenome-wide association study (MGWAS), and used it in a two-stage MGWAS analysis to better defining T2D-associated metagenomic markers. They sequenced the gut microbial DNA from 345 Chinese patients with T2D and identified approximately 60,000 T2D-associated markers that might be useful for detecting and characterizing T2D.
Of note, in addition to this new method and identification of T2D associated, researchers developed the concept of metagenomic linkage group (MLG) that allows easy classification and description of the abundant metagenomic data in a taxonomic form that can be used to replace traditional taxonomic classification approaches. MLG can provide metagenomic species-level information even for unknown species, including bacterial species-specific regions on a chromosome, and mobile genetic elements, such as plasmids and bacteriophages.
In general, the researchers found that healthy individuals typically had a higher number of butyrate-producing bacteria, which the researchers theorize may play a protective role against several types of diseases. In the T2D patients, that saw an increase in the number of, opportunistic pathogens, with the type of pathogen being quite diverse from patient to patient. Such changes in the gut bacteria composition have recently been reported for colorectal cancer patients and ageing population.
Junjie Qin, Primary Investigator on this project at BGI, said, "Gut microbiota has been widely considered as an important contributor to many kinds of chronic disease, like type 2 diabetes. However, it is still unclear on what and how exactly these commensal microbes contribute to human health. BGI, with a great power for conducting such a large-scale and in-depth studies, will continue to develop more sophisticated tools, collect a larger amount of scientific evidence, and better exploit the industrial/clinical potential in this field than has been done before."
Jun Wang, Executive Director of BGI, said, "As the human's 'second genome', the gut microbiome has a tight relationship with human health. High-throughput sequencing technologies and Metagenomics serve as robust tools for researchers to comprehensively explore the gut microbiota related with diseases, and shed new light into disease prevention and treatment. I believe the epoch of personalized medicine based on gut microbiome is not far away."
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- Junjie Qin, Yingrui Li, Zhiming Cai, Shenghui Li, Jianfeng Zhu, Fan Zhang, Suisha Liang, Wenwei Zhang, Yuanlin Guan, Dongqian Shen, Yangqing Peng, Dongya Zhang, Zhuye Jie, Wenxian Wu, Youwen Qin, Wenbin Xue, Junhua Li, Lingchuan Han, Donghui Lu, Peixian Wu, Yali Dai, Xiaojuan Sun, Zesong Li, Aifa Tang, Shilong Zhong, Xiaoping Li, Weineng Chen, Ran Xu, Mingbang Wang, Qiang Feng, Meihua Gong, Jing Yu, Yanyan Zhang, Ming Zhang, Torben Hansen, Gaston Sanchez, Jeroen Raes, Gwen Falony, Shujiro Okuda, Mathieu Almeida, Emmanuelle LeChatelier, Pierre Renault, Nicolas Pons, Jean-Michel Batto, Zhaoxi Zhang, Hua Chen, Ruifu Yang, Weimou Zheng, Songgang Li, Huanming Yang, Jian Wang, S. Dusko Ehrlich, Rasmus Nielsen, Oluf Pedersen, Karsten Kristiansen, Jun Wang. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 2012; DOI: 10.1038/nature11450
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