A metagenome-wide association study of gut microbiota in type 2 diabetes

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 and Jun Wang ()
Additional contact information
Junjie Qin: BGI-Shenzhen
Yingrui Li: BGI-Shenzhen
Zhiming Cai: Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University
Shenghui Li: BGI-Shenzhen
Jianfeng Zhu: BGI-Shenzhen
Fan Zhang: Peking University Shenzhen Hospital
Suisha Liang: BGI-Shenzhen
Wenwei Zhang: BGI-Shenzhen
Yuanlin Guan: BGI-Shenzhen
Dongqian Shen: BGI-Shenzhen
Yangqing Peng: BGI-Shenzhen
Dongya Zhang: BGI-Shenzhen
Zhuye Jie: BGI-Shenzhen
Wenxian Wu: BGI-Shenzhen
Youwen Qin: BGI-Shenzhen
Wenbin Xue: BGI-Shenzhen
Junhua Li: BGI-Shenzhen
Lingchuan Han: Peking University Shenzhen Hospital
Donghui Lu: Peking University Shenzhen Hospital
Peixian Wu: Peking University Shenzhen Hospital
Yali Dai: Peking University Shenzhen Hospital
Xiaojuan Sun: Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University
Zesong Li: Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University
Aifa Tang: Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University
Shilong Zhong: Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
Xiaoping Li: BGI-Shenzhen
Weineng Chen: BGI-Shenzhen
Ran Xu: BGI-Shenzhen
Mingbang Wang: BGI-Shenzhen
Qiang Feng: BGI-Shenzhen
Meihua Gong: BGI-Shenzhen
Jing Yu: BGI-Shenzhen
Yanyan Zhang: BGI-Shenzhen
Ming Zhang: BGI-Shenzhen
Torben Hansen: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark
Gaston Sanchez: University of California Berkeley
Jeroen Raes: VIB, 1050 Brussels, Belgium
Gwen Falony: VIB, 1050 Brussels, Belgium
Shujiro Okuda: VIB, 1050 Brussels, Belgium
Mathieu Almeida: Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France
Emmanuelle LeChatelier: Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France
Pierre Renault: Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France
Nicolas Pons: Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France
Jean-Michel Batto: Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France
Zhaoxi Zhang: BGI-Shenzhen
Hua Chen: BGI-Shenzhen
Ruifu Yang: BGI-Shenzhen
Weimou Zheng: BGI-Shenzhen
Songgang Li: BGI-Shenzhen
Huanming Yang: BGI-Shenzhen
Jian Wang: BGI-Shenzhen
S. Dusko Ehrlich: Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France
Rasmus Nielsen: University of California Berkeley
Oluf Pedersen: The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark
Karsten Kristiansen: BGI-Shenzhen
Jun Wang: BGI-Shenzhen

Nature, 2012, vol. 490, issue 7418, 55-60

Abstract: Abstract Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.

Date: 2012
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DOI: 10.1038/nature11450

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