Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease
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A system-level approach lays the foundation for a unique framework for studying the human microbiome, its organization, and its impact on human health, by integrating metagenomic data with an in silico systems-level analysis of metabolic networks.Abstract:
The human microbiome plays a key role in a wide range of host-related processes and has a profound effect on human health. Comparative analyses of the human microbiome have revealed substantial variation in species and gene composition associated with a variety of disease states but may fall short of providing a comprehensive understanding of the impact of this variation on the community and on the host. Here, we introduce a metagenomic systems biology computational framework, integrating metagenomic data with an in silico systems-level analysis of metabolic networks. Focusing on the gut microbiome, we analyze fecal metagenomic data from 124 unrelated individuals, as well as six monozygotic twin pairs and their mothers, and generate community-level metabolic networks of the microbiome. Placing variations in gene abundance in the context of these networks, we identify both gene-level and network-level topological differences associated with obesity and inflammatory bowel disease (IBD). We show that genes associated with either of these host states tend to be located at the periphery of the metabolic network and are enriched for topologically derived metabolic “inputs.” These findings may indicate that lean and obese microbiomes differ primarily in their interface with the host and in the way they interact with host metabolism. We further demonstrate that obese microbiomes are less modular, a hallmark of adaptation to low-diversity environments. We additionally link these topological variations to community species composition. The system-level approach presented here lays the foundation for a unique framework for studying the human microbiome, its organization, and its impact on human health.read more
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Journal ArticleDOI
Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013
Marie Ng,Tom P Fleming,Margaret Robinson,Blake Thomson,Nicholas Graetz,Christopher Margono,Erin C Mullany,Stan Biryukov,Cristiana Abbafati,Semaw Ferede Abera,Jerry Abraham,Niveen M E Abu-Rmeileh,Tom Achoki,Fadia AlBuhairan,Zewdie Aderaw Alemu,Rafael Alfonso,Mohammed K. Ali,Raghib Ali,Nelson Alvis Guzmán,Walid Ammar,Palwasha Anwari,Amitava Banerjee,Simón Barquera,Sanjay Basu,Derrick A Bennett,Zulfiqar A Bhutta,Jed D. Blore,N Cabral,Ismael Ricardo Campos Nonato,Jung-Chen Chang,Rajiv Chowdhury,Karen J. Courville,Michael H. Criqui,David K. Cundiff,Kaustubh Dabhadkar,Lalit Dandona,Lalit Dandona,Adrian Davis,Anand Dayama,Samath D Dharmaratne,Eric L. Ding,Adnan M. Durrani,Alireza Esteghamati,Farshad Farzadfar,Derek F J Fay,Valery L. Feigin,Abraham D. Flaxman,Mohammad H. Forouzanfar,Atsushi Goto,Mark A. Green,Rajeev Gupta,Nima Hafezi-Nejad,Graeme J. Hankey,Heather Harewood,Rasmus Havmoeller,Simon I. Hay,Lucia Hernandez,Abdullatif Husseini,Bulat Idrisov,Nayu Ikeda,Farhad Islami,Eiman Jahangir,Simerjot K. Jassal,Sun Ha Jee,Mona Jeffreys,Jost B. Jonas,Edmond K. Kabagambe,Shams Eldin Ali Hassan Khalifa,Andre Pascal Kengne,Yousef Khader,Young-Ho Khang,Daniel Kim,Ruth W Kimokoti,Jonas Minet Kinge,Yoshihiro Kokubo,Soewarta Kosen,Gene F. Kwan,Taavi Lai,Mall Leinsalu,Yichong Li,Xiaofeng Liang,Shiwei Liu,Giancarlo Logroscino,Paulo A. Lotufo,Yuan Qiang Lu,Jixiang Ma,Nana Kwaku Mainoo,George A. Mensah,Tony R. Merriman,Ali H. Mokdad,Joanna Moschandreas,Mohsen Naghavi,Aliya Naheed,Devina Nand,K.M. Venkat Narayan,Erica Leigh Nelson,Marian L. Neuhouser,Muhammad Imran Nisar,Takayoshi Ohkubo,Samuel Oti,Andrea Pedroza,Dorairaj Prabhakaran,Nobhojit Roy,Uchechukwu K.A. Sampson,Hyeyoung Seo,Sadaf G. Sepanlou,Kenji Shibuya,Rahman Shiri,Ivy Shiue,Gitanjali M Singh,Jasvinder A. Singh,Vegard Skirbekk,Nicolas J. C. Stapelberg,Lela Sturua,Bryan L. Sykes,Martin Tobias,Bach Xuan Tran,Leonardo Trasande,Hideaki Toyoshima,Steven van de Vijver,Tommi Vasankari,J. Lennert Veerman,Gustavo Velasquez-Melendez,Vasiliy Victorovich Vlassov,Stein Emil Vollset,Stein Emil Vollset,Theo Vos,Claire L. Wang,Xiao Rong Wang,Elisabete Weiderpass,Andrea Werdecker,Jonathan L. Wright,Y Claire Yang,Hiroshi Yatsuya,Jihyun Yoon,Seok Jun Yoon,Yong Zhao,Maigeng Zhou,Shankuan Zhu,Alan D. Lopez,Christopher J L Murray,Emmanuela Gakidou +141 more
TL;DR: The global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013 is estimated using a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs).
Journal ArticleDOI
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 Le-chatelier,Pierre Renault,Nicolas Pons,Jean-Michel Batto,Zhaoxi Zhang,Hua Chen,Ruifu Yang,Wei-Mou Zheng,Songgang Li,Huanming Yang,Jian Wang,S. Dusko Ehrlich,Rasmus Nielsen,Oluf Pedersen,Oluf Pedersen,Karsten Kristiansen,Jun Wang +56 more
TL;DR: 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.
Journal ArticleDOI
Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity
Amandine Everard,Clara Belzer,Lucie Geurts,Janneke P. Ouwerkerk,Céline Druart,Laure B. Bindels,Yves Guiot,Muriel Derrien,Giulio G. Muccioli,Nathalie M. Delzenne,Willem M. de Vos,Willem M. de Vos,Patrice D. Cani +12 more
TL;DR: Substantial insight is provided into the intricate mechanisms of bacterial regulation of the cross-talk between the host and gut microbiota and provides a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.
Journal ArticleDOI
Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice
Vanessa K. Ridaura,Jeremiah J. Faith,Federico E. Rey,Jiye Cheng,Alexis E. Duncan,Andrew L. Kau,Nicholas W. Griffin,Vincent Lombard,Bernard Henrissat,Bernard Henrissat,James R. Bain,Michael J. Muehlbauer,Olga Ilkayeva,Clay F. Semenkovich,Katsuhiko Funai,David K. Hayashi,Barbara J. Lyle,Margaret C. Martini,Luke K. Ursell,Jose C. Clemente,Will Van Treuren,William A. Walters,Rob Knight,Rob Knight,Christopher B. Newgard,Andrew C. Heath,Jeffrey I. Gordon +26 more
TL;DR: The results reveal that transmissible and modifiable interactions between diet and microbiota influence host biology and that adiposity is transmissible from human to mouse and that it was associated with changes in serum levels of branched-chain amino acids.
Journal ArticleDOI
The human microbiome: at the interface of health and disease
Ilseung Cho,Martin J. Blaser +1 more
TL;DR: The large-scale dynamics of the microbiome can be described by many of the tools and observations used in the study of population ecology, andiphering the metagenome and its aggregate genetic information can also be used to understand the functional properties of the microbial community.
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