Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease.

TitleMetagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease.
Publication TypeJournal Article
Year of Publication2012
AuthorsGreenblum, S, Turnbaugh, PJ, Borenstein, E
JournalProc Natl Acad Sci U S A
Volume109
Issue2
Pagination594-9
Date Published2012 Jan 10
ISSN1091-6490
KeywordsComputational Biology, Databases, Genetic, Feces, Gastrointestinal Tract, Humans, Inflammatory Bowel Diseases, Metabolic Networks and Pathways, Metagenome, Metagenomics, Obesity, Species Specificity, Statistics, Nonparametric, Systems Biology
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.

DOI10.1073/pnas.1116053109
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID22184244
PubMed Central IDPMC3258644
Grant ListP50 GM068763 / GM / NIGMS NIH HHS / United States
T32 HG00035 / HG / NHGRI NIH HHS / United States