{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:58:31Z","timestamp":1778273911729,"version":"3.51.4"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"7750","license":[{"start":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T00:00:00Z","timestamp":1553644800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2019,4]]},"DOI":"10.1038\/s41586-019-1065-y","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T19:51:07Z","timestamp":1553716267000},"page":"43-48","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":331,"title":["Structural variation in the gut microbiome associates with host health"],"prefix":"10.1038","volume":"568","author":[{"given":"David","family":"Zeevi","sequence":"first","affiliation":[]},{"given":"Tal","family":"Korem","sequence":"additional","affiliation":[]},{"given":"Anastasia","family":"Godneva","sequence":"additional","affiliation":[]},{"given":"Noam","family":"Bar","sequence":"additional","affiliation":[]},{"given":"Alexander","family":"Kurilshikov","sequence":"additional","affiliation":[]},{"given":"Maya","family":"Lotan-Pompan","sequence":"additional","affiliation":[]},{"given":"Adina","family":"Weinberger","sequence":"additional","affiliation":[]},{"given":"Jingyuan","family":"Fu","sequence":"additional","affiliation":[]},{"given":"Cisca","family":"Wijmenga","sequence":"additional","affiliation":[]},{"given":"Alexandra","family":"Zhernakova","sequence":"additional","affiliation":[]},{"given":"Eran","family":"Segal","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2019,3,27]]},"reference":[{"key":"1065_CR1","doi-asserted-by":"publisher","first-page":"S37","DOI":"10.1038\/ng2080","volume":"39","author":"SA McCarroll","year":"2007","unstructured":"McCarroll, S. A. & Altshuler, D. M. Copy-number variation and association studies of human disease. Nat. Genet. 39 (Suppl), S37\u2013S42 (2007).","journal-title":"Nat. Genet."},{"key":"1065_CR2","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1126\/science.1188308","volume":"329","author":"Y Taniguchi","year":"2010","unstructured":"Taniguchi, Y. et al. Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells. Science 329, 533\u2013538 (2010).","journal-title":"Science"},{"key":"1065_CR3","doi-asserted-by":"publisher","first-page":"8922","DOI":"10.1073\/pnas.95.15.8922","volume":"95","author":"EV Sokurenko","year":"1998","unstructured":"Sokurenko, E. V. et al. Pathogenic adaptation of Escherichia coli by natural variation of the FimH adhesin. Proc. Natl Acad. Sci. USA 95, 8922\u20138926 (1998).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1065_CR4","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.1128\/JB.187.7.2426-2438.2005","volume":"187","author":"SR Gill","year":"2005","unstructured":"Gill, S. R. et al. Insights on evolution of virulence and resistance from the complete genome analysis of an early methicillin-resistant Staphylococcus aureus strain and a biofilm-producing methicillin-resistant Staphylococcus epidermidis strain. J. Bacteriol. 187, 2426\u20132438 (2005).","journal-title":"J. Bacteriol."},{"key":"1065_CR5","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/nm.3145","volume":"19","author":"RA Koeth","year":"2013","unstructured":"Koeth, R. A. et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Med. 19, 576\u2013585 (2013).","journal-title":"Nature Med."},{"key":"1065_CR6","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1016\/j.cell.2017.05.036","volume":"169","author":"B Han","year":"2017","unstructured":"Han, B. et al. Microbial genetic composition tunes host longevity. Cell 169, 1249\u20131262 (2017).","journal-title":"Cell"},{"key":"1065_CR7","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.cell.2014.12.038","volume":"160","author":"S Greenblum","year":"2015","unstructured":"Greenblum, S., Carr, R. & Borenstein, E. Extensive strain-level copy-number variation across human gut microbiome species. Cell 160, 583\u2013594 (2015).","journal-title":"Cell"},{"key":"1065_CR8","doi-asserted-by":"publisher","first-page":"4523","DOI":"10.1073\/pnas.1006734107","volume":"108","author":"JR Swann","year":"2011","unstructured":"Swann, J. R. et al. Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. Proc. Natl Acad. Sci. USA 108 (Suppl 1), 4523\u20134530 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1065_CR9","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.copbio.2012.08.005","volume":"24","author":"JG LeBlanc","year":"2013","unstructured":"LeBlanc, J. G. et al. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr. Opin. Biotechnol. 24, 160\u2013168 (2013).","journal-title":"Curr. Opin. Biotechnol."},{"key":"1065_CR10","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1016\/j.cell.2015.10.048","volume":"163","author":"M Levy","year":"2015","unstructured":"Levy, M. et al. Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell 163, 1428\u20131443 (2015).","journal-title":"Cell"},{"key":"1065_CR11","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1016\/j.cell.2015.11.001","volume":"163","author":"D Zeevi","year":"2015","unstructured":"Zeevi, D. et al. Personalized nutrition by prediction of glycemic responses. Cell 163, 1079\u20131094 (2015).","journal-title":"Cell"},{"key":"1065_CR12","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nature11450","volume":"490","author":"J Qin","year":"2012","unstructured":"Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55\u201360 (2012).","journal-title":"Nature"},{"key":"1065_CR13","doi-asserted-by":"publisher","first-page":"17004","DOI":"10.1038\/nmicrobiol.2017.4","volume":"2","author":"J Halfvarson","year":"2017","unstructured":"Halfvarson, J. et al. Dynamics of the human gut microbiome in inflammatory bowel disease. Nature Microbiol. 2, 17004 (2017).","journal-title":"Nature Microbiol."},{"key":"1065_CR14","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1136\/gutjnl-2016-313235","volume":"66","author":"V Pascal","year":"2017","unstructured":"Pascal, V. et al. A microbial signature for Crohn\u2019s disease. Gut 66, 813\u2013822 (2017).","journal-title":"Gut"},{"key":"1065_CR15","doi-asserted-by":"publisher","first-page":"E4472","DOI":"10.1073\/pnas.1702302114","volume":"114","author":"S Rowan","year":"2017","unstructured":"Rowan, S. et al. Involvement of a gut\u2013retina axis in protection against dietary glycemia-induced age-related macular degeneration. Proc. Natl Acad. Sci. USA 114, E4472\u2013E4481 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1065_CR16","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/nbt.2942","volume":"32","author":"J Li","year":"2014","unstructured":"Li, J. et al. An integrated catalog of reference genes in the human gut microbiome. Nature Biotechnol. 32, 834\u2013841 (2014).","journal-title":"Nature Biotechnol."},{"key":"1065_CR17","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.chom.2016.12.014","volume":"21","author":"O Manor","year":"2017","unstructured":"Manor, O. & Borenstein, E. Systematic characterization and analysis of the taxonomic drivers of functional shifts in the human microbiome. Cell Host Microbe 21, 254\u2013267 (2017).","journal-title":"Cell Host Microbe"},{"key":"1065_CR18","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1038\/s41592-018-0176-y","volume":"15","author":"EA Franzosa","year":"2018","unstructured":"Franzosa, E. A. et al. Species-level functional profiling of metagenomes and metatranscriptomes. Nature Methods 15, 962\u2013968 (2018).","journal-title":"Nature Methods"},{"key":"1065_CR19","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/nrg2958","volume":"12","author":"C Alkan","year":"2011","unstructured":"Alkan, C., Coe, B. P. & Eichler, E. E. Genome structural variation discovery and genotyping. Nature Rev. Genet. 12, 363\u2013376 (2011).","journal-title":"Nature Rev. Genet."},{"key":"1065_CR20","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/j.cmet.2017.05.002","volume":"25","author":"T Korem","year":"2017","unstructured":"Korem, T. et al. Bread affects clinical parameters and induces gut microbiome-associated personal glycemic responses. Cell Metab. 25, 1243\u20131253 (2017).","journal-title":"Cell Metab."},{"key":"1065_CR21","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1126\/science.aad3369","volume":"352","author":"A Zhernakova","year":"2016","unstructured":"Zhernakova, A. et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352, 565\u2013569 (2016).","journal-title":"Science"},{"key":"1065_CR22","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/nature25973","volume":"555","author":"D Rothschild","year":"2018","unstructured":"Rothschild, D. et al. Environment dominates over host genetics in shaping human gut microbiota. Nature 555, 210\u2013215 (2018).","journal-title":"Nature"},{"key":"1065_CR23","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27\u201330 (2000).","journal-title":"Nucleic Acids Res."},{"key":"1065_CR24","doi-asserted-by":"publisher","first-page":"D754","DOI":"10.1093\/nar\/gkx1098","volume":"46","author":"DR Zerbino","year":"2018","unstructured":"Zerbino, D. R. et al. Ensembl 2018. Nucleic Acids Res. 46 (D1), D754\u2013D761 (2018).","journal-title":"Nucleic Acids Res."},{"key":"1065_CR25","doi-asserted-by":"publisher","unstructured":"El-Gebali, S. et al. The Pfam protein families database in 2019. Nucleic Acids Res. (2018). https:\/\/doi.org\/10.1093\/nar\/gky995","DOI":"10.1093\/nar\/gky995"},{"key":"1065_CR26","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1126\/science.aac4812","volume":"349","author":"T Korem","year":"2015","unstructured":"Korem, T. et al. Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples. Science 349, 1101\u20131106 (2015).","journal-title":"Science"},{"key":"1065_CR27","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1038\/35074106","volume":"410","author":"F Hayashi","year":"2001","unstructured":"Hayashi, F. et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099\u20131103 (2001).","journal-title":"Nature"},{"key":"1065_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01619-1","volume":"7","author":"Y Shen","year":"2017","unstructured":"Shen, Y. et al. Flagellar hooks and hook protein Flge participate in host microbe interactions at immunological level. Sci. Rep. 7, 1433 (2017).","journal-title":"Sci. Rep."},{"key":"1065_CR29","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1084\/jem.187.4.631","volume":"187","author":"JN Weiser","year":"1998","unstructured":"Weiser, J. N. et al. Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein. J. Exp. Med. 187, 631\u2013640 (1998).","journal-title":"J. Exp. Med."},{"key":"1065_CR30","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1111\/j.1365-2958.1990.tb00696.x","volume":"4","author":"JI Ross","year":"1990","unstructured":"Ross, J. I. et al. Inducible erythromycin resistance in staphylococci is encoded by a member of the ATP-binding transport super-gene family. Mol. Microbiol. 4, 1207\u20131214 (1990).","journal-title":"Mol. Microbiol."},{"key":"1065_CR31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043052","volume":"7","author":"ML Zupancic","year":"2012","unstructured":"Zupancic, M. L. et al. Analysis of the gut microbiota in the old order Amish and its relation to the metabolic syndrome. PLoS One 7, e43052 (2012).","journal-title":"PLoS One"},{"key":"1065_CR32","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nature12198","volume":"498","author":"FH Karlsson","year":"2013","unstructured":"Karlsson, F. H. et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 498, 99\u2013103 (2013).","journal-title":"Nature"},{"key":"1065_CR33","doi-asserted-by":"publisher","first-page":"10415","DOI":"10.1074\/jbc.M708043200","volume":"283","author":"K Yoshida","year":"2008","unstructured":"Yoshida, K. et al. myo-Inositol catabolism in Bacillus subtilis. J. Biol. Chem. 283, 10415\u201310424 (2008).","journal-title":"J. Biol. Chem."},{"key":"1065_CR34","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1152\/physrev.1990.70.2.567","volume":"70","author":"EN Bergman","year":"1990","unstructured":"Bergman, E. N. Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol. Rev. 70, 567\u2013590 (1990).","journal-title":"Physiol. Rev."},{"key":"1065_CR35","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/NEJM198901053200105","volume":"320","author":"JM Harig","year":"1989","unstructured":"Harig, J. M., Soergel, K. H., Komorowski, R. A. & Wood, C. M. Treatment of diversion colitis with short-chain-fatty acid irrigation. N. Engl. J. Med. 320, 23\u201328 (1989).","journal-title":"N. Engl. J. Med."},{"key":"1065_CR36","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.2337\/db08-1637","volume":"58","author":"Z Gao","year":"2009","unstructured":"Gao, Z. et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58, 1509\u20131517 (2009).","journal-title":"Diabetes"},{"key":"1065_CR37","doi-asserted-by":"publisher","first-page":"D529","DOI":"10.1093\/nar\/gkw989","volume":"45","author":"DR Mende","year":"2017","unstructured":"Mende, D. R. et al. proGenomes: a resource for consistent functional and taxonomic annotations of prokaryotic genomes. Nucleic Acids Res. 45 (D1), D529\u2013D534 (2017).","journal-title":"Nucleic Acids Res."},{"key":"1065_CR38","doi-asserted-by":"publisher","first-page":"2864","DOI":"10.1038\/ismej.2017.126","volume":"11","author":"MR Olm","year":"2017","unstructured":"Olm, M. R., Brown, C. T., Brooks, B. & Banfield, J. F. dRep: a tool for fast and accurate genomic comparisons that enables improved genome recovery from metagenomes through de-replication. ISME J. 11, 2864\u20132868 (2017).","journal-title":"ISME J."},{"key":"1065_CR39","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1038\/nmeth.2221","volume":"9","author":"S Marco-Sola","year":"2012","unstructured":"Marco-Sola, S., Sammeth, M., Guig\u00f3, R. & Ribeca, P. The GEM mapper: fast, accurate and versatile alignment by filtration. Nat. Methods 9, 1185\u20131188 (2012).","journal-title":"Nat. Methods"},{"key":"1065_CR40","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1038\/nmeth.3589","volume":"12","author":"DT Truong","year":"2015","unstructured":"Truong, D. T. et al. MetaPhlAn2 for enhanced metagenomic taxonomic profiling. Nat. Methods 12, 902\u2013903 (2015).","journal-title":"Nat. Methods"},{"key":"1065_CR41","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-3-r46","volume":"15","author":"DE Wood","year":"2014","unstructured":"Wood, D. E. & Salzberg, S. L. Kraken: ultrafast metagenomic sequence classification using exact alignments. Genome Biol. 15, R46 (2014).","journal-title":"Genome Biol."},{"key":"1065_CR42","volume":"3","author":"J Lu","year":"2017","unstructured":"Lu, J., Breitwieser, F. P., Thielen, P. & Salzberg, S. L. Bracken: estimating species abundance in metagenomics data. Peer. J. Comput. Sci. 3, e104 (2017).","journal-title":"J. Comput. Sci."},{"key":"1065_CR43","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nmeth.3176","volume":"12","author":"B Buchfink","year":"2015","unstructured":"Buchfink, B., Xie, C. & Huson, D. H. Fast and sensitive protein alignment using DIAMOND. Nat. Methods 12, 59\u201360 (2015).","journal-title":"Nat. Methods"},{"key":"1065_CR44","doi-asserted-by":"publisher","first-page":"W200","DOI":"10.1093\/nar\/gky448","volume":"46","author":"SC Potter","year":"2018","unstructured":"Potter, S. C. et al. HMMER web server: 2018 update. Nucleic Acids Res. 46, W200\u2013W204 (2018).","journal-title":"Nucleic Acids Res."},{"key":"1065_CR45","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57, 289\u2013300 (1995).","journal-title":"J. R. Stat. Soc. B"},{"key":"1065_CR46","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nature13793","volume":"514","author":"J Suez","year":"2014","unstructured":"Suez, J. et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, 181\u2013186 (2014).","journal-title":"Nature"},{"key":"1065_CR47","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1038\/nmeth.4458","volume":"14","author":"A Sczyrba","year":"2017","unstructured":"Sczyrba, A. et al. Critical Assessment of Metagenome Interpretation \u2013 a benchmark of metagenomics software. Nat. Methods 14, 1063\u20131071 (2017).","journal-title":"Nat. Methods"},{"key":"1065_CR48","doi-asserted-by":"crossref","unstructured":"Liu, B., Gibbons, T., Ghodsi, M. & Pop, M. MetaPhyler: taxonomic profiling for metagenomic sequences. 2010 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) 95\u2013100 (IEEE, 2010).","DOI":"10.1109\/BIBM.2010.5706544"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41586-019-1065-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-019-1065-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-019-1065-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T06:01:43Z","timestamp":1721109703000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-019-1065-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,27]]},"references-count":48,"journal-issue":{"issue":"7750","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["1065"],"URL":"https:\/\/doi.org\/10.1038\/s41586-019-1065-y","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,27]]},"assertion":[{"value":"27 February 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 February 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}