Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease
Open accessAbstract
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.
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Obesity is associated with a significant decrease in gut microbiota diversity.
“Obesity has been associated with a significant decrease in the diversity of the gut microbiota.81, 82”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [82]
Cites
An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444 · see citing works
Self-citationModularity and community structure in networks
Newman, M. E. J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601602103 · Cited by 12,256 · see citing works
A human gut microbial gene catalogue established by metagenomic sequencing
MetaHIT Consortium, Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., et al. (2010) · Nature · doi:10.1038/nature08821 · Cited by 11,624 · see citing works
A core gut microbiome in obese and lean twins
Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., et al. (2009) · Nature · doi:10.1038/nature07540 · Cited by 7,823 · see citing works
Self-citationTurnbaugh, P. J., Ley, R. E., Hamady, M., Fraser-Liggett, C. M., Knight, R., & Gordon, J. I. (2007) · Nature · doi:10.1038/nature06244 · Cited by 6,091 · see citing works
Self-citationThe Large-Scale Organization of Metabolic Networks
Jeong, H., Tombor, B., Albert, R., Oltvai, Z. N., & Barabási, A.-L. (2000) · Nature · doi:10.1038/35036627 · Cited by 4,972 · see citing works
Metagenomic Analysis of the Human Distal Gut Microbiome
Gill, S. R., Pop, M., DeBoy, R. T., Eckburg, P. B., Turnbaugh, P. J., Samuel, B. S., Gordon, J. I., Relman, D. A., Fraser-Liggett, C. M., & Nelson, K. E. (2006) · Science · doi:10.1126/science.1124234 · Cited by 4,699 · see citing works
Self-citationFunctional cartography of complex metabolic networks
Guimerà, R., & Nunes Amaral, L. A. (2005) · Nature · doi:10.1038/nature03288 · Cited by 3,983 · cited 1× · see citing works
“regulation (24, 25), modularity (26, 27), essentiality and mutant viability (28), genetic and environmental robustness (29), adaptation (30, 31), and species interaction (32).”
BackgroundEcological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine
Ley, R. E., Peterson, D. A., & Gordon, J. I. (2006) · Cell · doi:10.1016/j.cell.2006.02.017 · Cited by 3,358 · see citing works
From genomics to chemical genomics: new developments in KEGG
Kanehisa, M. I. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj102 · Cited by 3,126 · see citing works
The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice
Turnbaugh, P. J., Ridaura, V. K., Faith, J. J., Rey, F. E., Knight, R., & Gordon, J. I. (2009) · Science Translational Medicine · doi:10.1126/scitranslmed.3000322 · Cited by 3,058 · see citing works
Self-citationThe NIH Human Microbiome ProjectPreprint
The NIH HMP Working Group, Peterson, J. L., Garges, S., Giovanni, M. Y., McInnes, P., Wang, L., Schloss, J. A., Bonazzi, V. R., McEwen, J. E., Wetterstrand, K. A., et al. (2009) · Genome Research · doi:10.1101/gr.096651.109 · Cited by 2,092 · see citing works
Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5
Vijay-Kumar, M., Aitken, J. D., Carvalho, F. A., Cullender, T. C., Mwangi, S., Srinivasan, S., Sitaraman, S. V., Knight, R., Ley, R. E., & Gewirtz, A. T. (2010) · Science · doi:10.1126/science.1179721 · Cited by 2,068 · see citing works
The Subsystems Approach to Genome Annotation and its Use in the Project to Annotate 1000 Genomes
Overbeek, R. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki866 · Cited by 2,019 · see citing works
Computing topological parameters of biological networks
Assenov, Y., Ramírez, F., Schelhorn, S.-E., Lengauer, T., & Albrecht, M. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm554 · Cited by 1,805 · see citing works
Comparative Metagenomics of Microbial Communities
Tringe, S. G., von Mering, C., Kobayashi, A., Salamov, A. A., Chen, K., Chang, H. W., Podar, M., Short, J. M., Mathur, E. J., Detter, J. C., et al. (2005) · Science · doi:10.1126/science.1107851 · Cited by 1,694 · see citing works
An ecological and evolutionary perspective on human–microbe mutualism and disease
Dethlefsen, L., McFall-Ngai, M., & Relman, D. A. (2007) · Nature · doi:10.1038/nature06245 · Cited by 1,660 · see citing works
Worlds within worlds: evolution of the vertebrate gut microbiota
Ley, R. E., Lozupone, C., Hamady, M., Knight, R. D., & Gordon, J. I. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1978 · Cited by 1,652 · see citing works
Statistical Methods for Detecting Differentially Abundant Features in Clinical Metagenomic Samples
White, J. R., Nagarajan, N., & Pop, M. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000352 · Cited by 1,581 · see citing works
Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes
Kurokawa, K., Itoh, T., Kuwahara, T., Oshima, K., Toh, H., Toyoda, A., Takami, H., Morita, H., Sharma, V. K., Srivastava, T. P., et al. (2007) · DNA Research · doi:10.1093/dnares/dsm018 · Cited by 869 · see citing works
Applications of genome‐scale metabolic reconstructions
Oberhardt, M., Palsson, B. Ø., & Papin, J. A. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.77 · Cited by 820 · see citing works
Metabolic network structure determines key aspects of functionality and regulation
Stelling, J., Klamt, S., Bettenbrock, K., Schuster, S., & Gilles, E. D. (2002) · Nature · doi:10.1038/nature01166 · Cited by 802 · see citing works
Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla
Mahowald, M. A., Rey, F. E., Seedorf, H., Turnbaugh, P. J., Fulton, R. S., Wollam, A., Shah, N., Wang, C., Magrini, V. J., Wilson, R. K., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901529106 · Cited by 737 · see citing works
Self-citationUncovering transcriptional regulation of metabolism by using metabolic network topology
Patil, K. R., & NIELSEN, J. K. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406811102 · Cited by 649 · see citing works
Khoruts, A., Dicksved, J., Jansson, J. K., & Sadowsky, M. J. (2010) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e3181c87e02 · Cited by 649 · see citing works
Herrgård, M. J., Swainston, N., Dobson, P., Dunn, W. B., Arga, K. Y., Arvas, M., Blüthgen, N., Borger, S., Costenoble, R., Heinemann, M., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1492 · Cited by 588 · see citing works
Metabolic modeling of a mutualistic microbial community
Stolyar, S. M., Dien, S. V., Hillesland, K. L., Pinel, N., Lie, T. J., Leigh, J. A., & Stahl, D. A. (2007) · Molecular Systems Biology · doi:10.1038/msb4100131 · Cited by 553 · see citing works
Nitric oxide in inflammatory bowel disease: a universal messenger in an unsolved puzzle
Kolios, G. C., Valatas, V., & Ward, S. G. (2004) · Immunology · doi:10.1111/j.1365-2567.2004.01984.x · Cited by 541 · see citing works
Lederberg, J. (2000) · Science · doi:10.1126/science.288.5464.287 · Cited by 523 · see citing works
Adaptive evolution of bacterial metabolic networks by horizontal gene transfer
Pál, C., Papp, B., & Lercher, M. J. (2005) · Nature Genetics · doi:10.1038/ng1686 · Cited by 505 · see citing works
The Effect of Oxygen on Biochemical Networks and the Evolution of Complex Life
Raymond, J., & Segrè, D. (2006) · Science · doi:10.1126/science.1118439 · Cited by 494 · see citing works
Molecular eco-systems biology: towards an understanding of community function
Raes, J., & Peer Bork, B. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1935 · Cited by 397 · see citing works
Emergent cooperation in microbial metabolism
Wintermute, E. H., & Silver, P. A. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.66 · Cited by 349 · see citing works
Human gut microbiome adopts an alternative state following small bowel transplantation
Hartman, A., Lough, D., Barupal, D. K., Fiehn, O., Fishbein, T., ZASLOFF, M. A., & Eisen, J. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904847106 · Cited by 341 · see citing works
Environments that Induce Synthetic Microbial Ecosystems
Klitgord, N., & Segrè, D. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1001002 · Cited by 331 · see citing works
The large-scale organization of the bacterial network of ecological co-occurrence interactions
Freilich, S., Kreimer, A., Meilijson, I., Gophna, U., Sharan, R., & Ruppin, E. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq118 · Cited by 313 · see citing works
Postprandial remodeling of the gut microbiota in Burmese pythons
Costello, E. K., Gordon, J. I., Secor, S. M., & Knight, R. D. (2010) · The ISME Journal · doi:10.1038/ismej.2010.71 · Cited by 267 · see citing works
Large-scale reconstruction and phylogenetic analysis of metabolic environments
Borenstein, E., Kupiec, M., Feldman, M. W., & Ruppin, E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806162105 · Cited by 238 · see citing works
Self-citationTepper, N., & Shlomi, T. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp704 · Cited by 238 · see citing works
The evolution of modularity in bacterial metabolic networks
Kreimer, A., Borenstein, E., Gophna, U., & Ruppin, E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712149105 · Cited by 210 · see citing works
Self-citationQuantifying environmental adaptation of metabolic pathways in metagenomics
Gianoulis, T. A., Raes, J., Patel, P. V., Bjornson, R. D., Korbel, J. O., Letunić, I., Yamada, T., Paccanaro, A., Jensen, L. J., Snyder, M. P., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808022106 · Cited by 204 · see citing works
Environmental variability and modularity of bacterial metabolic networks
Parter, M., Kashtan, N., & Alon, U. S. (2007) · BMC Evolutionary Biology · doi:10.1186/1471-2148-7-169 · Cited by 201 · see citing works
Gil‐Ortega, M., Stucchi, P., Guzmán‐Ruiz, R., Cano, V., Arribas, S. M., González, M. C., Ruiz‐Gayo, M., Fernández‐Alfonso, M. S., & Somoza, B. (2010) · Endocrinology · doi:10.1210/en.2009-1464 · Cited by 118 · see citing works
Metabolic-network-driven analysis of bacterial ecological strategies
Freilich, S., Kreimer, A., Borenstein, E., Yosef, N., Sharan, R., Gophna, U., & Ruppin, E. (2009) · Genome biology · doi:10.1186/gb-2009-10-6-r61 · Cited by 98 · see citing works
Self-citationStructural correlations in bacterial metabolic networks
Bernhardsson, S., Gerlee, P., & Lizana, L. (2011) · BMC Evolutionary Biology · doi:10.1186/1471-2148-11-20 · Cited by 94 · see citing works
The outcomes of pathway database computations depend on pathway ontology
Green, M. L. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl438 · Cited by 85 · see citing works
Topological Signatures of Species Interactions in Metabolic Networks
Borenstein, E., & Feldman, M. W. (2009) · Journal of Computational Biology · doi:10.1089/cmb.2008.06tt · Cited by 79 · see citing works
Self-citationFunctional essentiality from topology features in metabolic networks: A case study in yeast
Palumbo, M. C., Colosimo, A., Giuliani, A., & Farina, L. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.07.033 · Cited by 71 · see citing works
Chen, C., Sullivan, S. D., Anderson, T., Tan, A. C., Alex, P., Brant, S. R., Cuffari, C., Bayless, T. M., Talor, M. V., Burek, C. L., et al. (2009) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m800593-mcp200 · Cited by 68 · see citing works
Reconstruction annotation jamborees: a community approach to systems biology
Thiele, I., & Palsson, B. Ø. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.15 · Cited by 65 · see citing works
A rendezvous with our microbes
Gordon, J. I., & Klaenhammer, T. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101958108 · Cited by 57 · see citing works
Induced Nitric Oxide Synthase as a Major Player in the Oncogenic Transformation of Inflamed Tissue
Yang, G., Taboada, S., & Liao, J. (2009) · Methods in molecular biology · doi:10.1007/978-1-60327-530-9_8 · Cited by 56 · see citing works
The PTS transporters of Lactobacillus gasseri ATCC 33323
Francl, A. L., Thongaram, T., & Miller, M. J. (2010) · BMC Microbiology · doi:10.1186/1471-2180-10-77 · Cited by 53 · see citing works
Decoupling Environment-Dependent and Independent Genetic Robustness across Bacterial Species
Freilich, S., Kreimer, A., Borenstein, E., Gophna, U., Sharan, R., & Ruppin, E. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000690 · Cited by 38 · see citing works
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Ng, M., Fleming, T., Robinson, M., Thomson, B., Graetz, N., Margono, C., Mullany, E. C., Biryukov, S., Abbafati, C., Abera, S. F., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60460-8 · Cited by 11,952 · see citing works
A metagenome-wide association study of gut microbiota in type 2 diabetes
Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., et al. (2012) · Nature · doi:10.1038/nature11450 · Cited by 6,762 · see citing works
Everard, A., Belzer, C., Geurts, L., Ouwerkerk, J. P., Druart, C., Bindels, L. B., Guiot, Y., Derrien, M., Muccioli, G. G., Delzenne, N. M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219451110 · Cited by 4,511 · see citing works
Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice
Ridaura, V. K., Faith, J. J., Rey, F. E., Cheng, J., Duncan, A. E., Kau, A. L., Griffin, N. W., Lombard, V., Henrissat, B., Bain, J. R., et al. (2013) · Science · doi:10.1126/science.1241214 · Cited by 3,788 · see citing works
Gut microbiota functions: metabolism of nutrients and other food components
Rowland, I., Gibson, G., Heinken, A., Scott, K., Swann, J., Thiele, I., & Tuohy, K. (2018) · European Journal of Nutrition · doi:10.1007/s00394-017-1445-8 · Cited by 2,878 · see citing works
Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment
Morgan, X. C., Tickle, T. L., Sokol, H., Gevers, D., Devaney, K. L., Ward, D. V., Reyes, J. A., Shah, S. A., LeLeiko, N., Snapper, S. B., et al. (2012) · Genome Biology · doi:10.1186/gb-2012-13-9-r79 · Cited by 2,713 · see citing works
Influence of diet on the gut microbiome and implications for human health
Singh, R. K., Chang, H.-W., Yan, D., Lee, K. M., Ucmak, D., Wong, K., Abrouk, M., Farahnik, B., Nakamura, M., Zhu, T. H., et al. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-017-1175-y · Cited by 2,599 · see citing works
Alterations of the human gut microbiome in liver cirrhosis
Qin, N., Yang, F., Li, A., Prifti, E., Chen, Y., Shao, L., Guo, J., Le Chatelier, E., Yao, J., Wu, L., et al. (2014) · Nature · doi:10.1038/nature13568 · Cited by 2,177 · see citing works
Host Remodeling of the Gut Microbiome and Metabolic Changes during Pregnancy
Koren, O., Goodrich, J. K., Cullender, T. C., Spor, A., Laitinen, K., Kling Bäckhed, H., Gonzalez, A., Werner, J. J., Angenent, L. T., Knight, R., et al. (2012) · Cell · doi:10.1016/j.cell.2012.07.008 · Cited by 2,165 · see citing works
The Microbiome in Inflammatory Bowel Disease: Current Status and the Future Ahead
Kostic, A. D., Xavier, R. J., & Gevers, D. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.02.009 · Cited by 1,789 · see citing works
Dietary fiber and prebiotics and the gastrointestinal microbiota
Holscher, H. D. (2017) · Gut Microbes · doi:10.1080/19490976.2017.1290756 · Cited by 1,808 · see citing works
Gut microbiota dysbiosis contributes to the development of hypertension
Li, J., Zhao, F., Wang, Y., Chen, J., Tao, J., Tian, G., Wu, S., Liu, W., Cui, Q., Geng, B., et al. (2017) · Microbiome · doi:10.1186/s40168-016-0222-x · Cited by 1,685 · see citing works
Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease
Pickard, J. M., Zeng, M. Y., Caruso, R., & Núñez, G. (2017) · Immunological Reviews · doi:10.1111/imr.12567 · Cited by 1,699 · see citing works
Mining electronic health records: towards better research applications and clinical care
Jensen, P. B., Jensen, L. J., & Brunak, S. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3208 · Cited by 1,680 · see citing works
Symptomatic atherosclerosis is associated with an altered gut metagenome
Karlsson, F. H., Fåk, F., Nookaew, I., Tremaroli, V., Fagerberg, B., Petranovic, D., Bäckhed, F., & Nielsen, J. (2012) · Nature Communications · doi:10.1038/ncomms2266 · Cited by 1,371 · see citing works
Probiotics, gut microbiota, and their influence on host health and disease
Sánchez, B., Delgado, S., Blanco‐Míguez, A., Lourenço, A., Gueimonde, M., & Margolles, A. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600240 · Cited by 1,104 · see citing works
Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity
Liou, A. P., Paziuk, M., Luevano, J.-M., Machineni, S., Turnbaugh, P. J., & Kaplan, L. M. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005687 · Cited by 1,007 · see citing works
Self-citationCharacterization of the gut microbiome using 16S or shotgun metagenomics
Jovel, J., Patterson, J., Wang, W., Hotte, N., O'Keefe, S., Mitchel, T., Perry, T., Kao, D., Mason, A. L., Madsen, K. L., et al. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00459 · Cited by 942 · see citing works
An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis
Chen, J., Wright, K., Davis, J. M., Jeraldo, P., Marietta, E. V., Murray, J., Nelson, H., Matteson, E. L., & Taneja, V. (2016) · Genome Medicine · doi:10.1186/s13073-016-0299-7 · Cited by 858 · see citing works
Generation of genome-scale metabolic reconstructions for 773 members of the human gut microbiota
Magnúsdóttir, S., Heinken, A., Kutt, L., Ravcheev, D. A., Bauer, E., Noronha, A., Greenhalgh, K., Jäger, C., Baginska, J., Wilmes, P., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.3703 · Cited by 798 · see citing works
Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer
Song, M., Chan, A. T., & Sun, J. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.06.048 · Cited by 752 · see citing works
Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity
Everard, A., Lazarevic, V., Gaïa, N., Johansson, M., Ståhlman, M., Backhed, F., Delzenne, N. M., Schrenzel, J., François, P., & Cani, P. D. (2014) · The ISME Journal · doi:10.1038/ismej.2014.45 · Cited by 598 · see citing works
Specialized metabolites from the microbiome in health and disease
Sharon, G., Garg, N., Debelius, J., Knight, R., Dorrestein, P. C., & Mazmanian, S. K. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.016 · Cited by 544 · see citing works
Microbial shifts in the aging mouse gut
Langille, M. G., Meehan, C. J., Koenig, J. E., Dhanani, A. S., Rose, R. A., Howlett, S. E., & Beiko, R. G. (2014) · Microbiome · doi:10.1186/s40168-014-0050-9 · Cited by 437 · see citing works
Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer
Cani, P. D., & Jordan, B. F. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0025-6 · Cited by 383 · see citing works
A predictive index for health status using species-level gut microbiome profiling
Gupta, V. K., Kim, M., Bakshi, U., Cunningham, K. Y., Davis, J. M., Lazaridis, K. N., Nelson, H., Chia, N., & Sung, J. (2020) · Nature Communications · doi:10.1038/s41467-020-18476-8 · Cited by 338 · see citing works
Genetics and Pathogenesis of Inflammatory Bowel Disease
Liu, T.-C., & Stappenbeck, T. S. (2016) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044152 · Cited by 289 · see citing works
Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice
Ritze, Y., Bárdos, G., Claus, A., Ehrmann, V., Bergheim, I., Schwiertz, A., & Bischoff, S. C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0080169 · Cited by 292 · see citing works
Fecal microbiota transplantation broadening its application beyond intestinal disorders
Xu, M.-Q. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i1.102 · Cited by 231 · see citing works
Morton, E. R., Lynch, J., Froment, A., Lafosse, S., Heyer, E., Przeworski, M., Blekhman, R., & Ségurel, L. (2015) · PLOS Genetics · doi:10.1371/journal.pgen.1005658 · Cited by 231 · see citing works
Big data in IBD: big progress for clinical practice
Seyed Tabib, N. S., Madgwick, M., Sudhakar, P., Verstockt, B., Korcsmaros, T., & Vermeire, S. (2020) · Gut · doi:10.1136/gutjnl-2019-320065 · Cited by 223 · see citing works
The role of environmental factors in modulating immune responses in early life
MacGillivray, D. M., & Kollmann, T. R. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00434 · Cited by 219 · see citing works
Microbiome profiling reveals gut dysbiosis in a transgenic mouse model of Huntington's disease
Kong, G., Cao, K.-A. L., Judd, L. M., Li, S., Renoir, T., & Hannan, A. J. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.09.001 · Cited by 212 · see citing works
Epigenetic Regulation at the Interplay Between Gut Microbiota and Host Metabolism
Miro-Blanch, J., & Yanes, O. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00638 · Cited by 195 · see citing works
Nasko, D. J., Koren, S., Phillippy, A. M., & Treangen, T. J. (2018) · Genome Biology · doi:10.1186/s13059-018-1554-6 · Cited by 170 · see citing works
Li, Q., Lauber, C. L., Czarnecki-Maulden, G., Pan, Y., & Hannah, S. S. (2017) · mBio · doi:10.1128/mbio.01703-16 · Cited by 148 · see citing works
Gut microbiome of an 11th Century A.D. pre-Columbian Andean mummy
Santiago-Rodriguez, T. M., Fornaciari, G., Luciani, S., Dowd, S. E., Toranzos, G. A., Marota, I., & Cano, R. J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0138135 · Cited by 123 · see citing works
Modeling metabolism of the human gut microbiome
Magnúsdóttir, S., & Thiele, I. (2018) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2017.12.005 · Cited by 127 · see citing works
Metabolic network modeling of microbial communities
Biggs, M. B., Medlock, G. L., Kolling, G. L., & Papin, J. A. (2015) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1308 · Cited by 124 · see citing works
Ruiz, A., Cerdó, T., Jáuregui, R., Pieper, D. H., Marcos, A., Clemente, A., García, F., Margolles, A., Ferrer, M., Campoy, C., et al. (2017) · Environmental Microbiology · doi:10.1111/1462-2920.13713 · Cited by 85 · see citing works
Fang, S., Xiong, X., Su, Y., Huang, L., & Chen, C. (2017) · BMC Microbiology · doi:10.1186/s12866-017-1055-x · Cited by 80 · see citing works
- Authors
- Greenblum, S., Turnbaugh, P. J., & Borenstein, E.
- Affiliations
- University of Washington (US)
- Harvard University (US)
- Santa Fe Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-12-19
- Volume
- 109
- Issue
- 2
- Pages
- 594-599
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3258644
- OpenAlex
- W2088209062
- Cited by
- 821
- References
- 54
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 39 · 2023: 40 · 2022: 50 · 2021: 73 · 2020: 79 · 2019: 49 · 2018: 50 · 2017: 79 · 2016: 64 · 2015: 77 · 2014: 80 · 2013: 62 · 2012: 39
- FWCI
- 23.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (GM068763)
- National Human Genome Research Institute (T32HG000035)
- National Institute of General Medical Sciences (P50GM068763)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- human gut microbiome, obesity, inflammatory bowel disease, microbial metabolic networks, network topology, network modularity, monozygotic twins, host-microbe interactions, microbial community composition, gene abundance
- MeSH terms
- Feces, Humans, Obesity, Species Specificity, Inflammatory Bowel Diseases, Statistics, Nonparametric, Computational Biology, Databases, Genetic, Gastrointestinal Tract, Systems Biology, Metabolic Networks and Pathways, Metagenome, Metagenomics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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