Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors
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In vertebrates, including humans, individuals harbor gut microbial communities whose species composition and relative proportions of dominant microbial groups are tremendously varied. Although external and stochastic factors clearly contribute to the individuality of the microbiota, the fundamental principles dictating how environmental factors and host genetic factors combine to shape this complex ecosystem are largely unknown and require systematic study. Here we examined factors that affect microbiota composition in a large ( n = 645) mouse advanced intercross line originating from a cross between C57BL/6J and an ICR-derived outbred line (HR). Quantitative pyrosequencing of the microbiota defined a core measurable microbiota (CMM) of 64 conserved taxonomic groups that varied quantitatively across most animals in the population. Although some of this variation can be explained by litter and cohort effects, individual host genotype had a measurable contribution. Testing of the CMM abundances for cosegregation with 530 fully informative SNP markers identified 18 host quantitative trait loci (QTL) that show significant or suggestive genome-wide linkage with relative abundances of specific microbial taxa. These QTL affect microbiota composition in three ways; some loci control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. These data provide clear evidence for the importance of host genetic control in shaping individual microbiome diversity in mammals, a key step toward understanding the factors that govern the assemblages of gut microbiota associated with complex diseases.
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Differences in microbiome diversity are partially attributed to genotype and sex.
“Differences in microbiome diversity have been shown to be partially attributed by genotype and sex [79–83].”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [79]
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Naive Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial Taxonomy
Wang, Q., Garrity, G. M., Tiedje, J. M., & Cole, J. R. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.00062-07 · Cited by 19,770 · see citing works
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
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
The gut microbiota as an environmental factor that regulates fat storage
Bäckhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., Nagy, A., Semenkovich, C. F., & Gordon, J. I. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407076101 · Cited by 6,245 · see citing works
Obesity alters gut microbial ecology
Ley, R. E., Bäckhed, F., Turnbaugh, P., Lozupone, C. A., Knight, R. D., & Gordon, J. I. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504978102 · Cited by 6,176 · see citing works
Frank, D. N., St. Amand, A. L., Feldman, R. A., Boedeker, E. C., Harpaz, N., & Pace, N. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706625104 · Cited by 4,611 · see citing works
Evolution of mammals and their gut microbes
Ley, R. E., Hamady, M., Lozupone, C., Turnbaugh, P. J., Ramey, R. R., Bircher, J. S., Schlegel, M. L., Tucker, T. A., Schrenzel, M. D., Knight, R., et al. (2008) · Science · doi:10.1126/science.1155725 · Cited by 3,747 · see citing works
Ecological 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
Self-citationAn Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System
Mazmanian, S. K., Liu, C. H., Tzianabos, A. O., & Kasper, D. L. (2005) · Cell · doi:10.1016/j.cell.2005.05.007 · Cited by 2,910 · see citing works
Development of the Human Infant Intestinal Microbiota
Palmer, C., Bik, E. M., DiGiulio, D. B., Relman, D. A., & Brown, P. O. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050177 · Cited by 2,877 · see citing works
The Wellcome Trust Case Control Consortium, U.K.
Mossman, K. (2008) · Scientific American · doi:10.1038/scientificamerican0108-42a · Cited by 2,714 · see citing works
A microbial symbiosis factor prevents intestinal inflammatory disease
Mazmanian, S. K., Round, J. L., & Kasper, D. L. (2008) · Nature · doi:10.1038/nature07008 · Cited by 2,340 · 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
Innate immunity and intestinal microbiota in the development of Type 1 diabetes
Wen, L., Ley, R. E., Volchkov, P. Y., Stranges, P. B., Avanesyan, L., Stonebraker, A. C., Hu, C., Wong, F. S., Szot, G. L., Bluestone, J. A., et al. (2008) · Nature · doi:10.1038/nature07336 · Cited by 1,921 · see citing works
Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens
Zheng, Y., Valdez, P. A., Danilenko, D. M., Hu, Y., Susan, M. L., Gong, Q., Abbas, A. R., Modrusan, Z. D., Ghilardi, N., de Sauvage, F. J., et al. (2008) · Nature Medicine · doi:10.1038/nm1720 · Cited by 1,910 · 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
Developmental microbial ecology of the neonatal gastrointestinal tract
Mackie, R. I., Sghir, A., & Gaskins, H. R. (1999) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.5.1035s · Cited by 1,360 · see citing works
Parkes, M., Barrett, J. C., Prescott, N. J., Tremelling, M., Anderson, C. A., Fisher, S. A., Roberts, R. G., Nimmo, E. R., Cummings, F. J. R., Soars, D., et al. (2007) · Nature Genetics · doi:10.1038/ng2061 · Cited by 1,144 · see citing works
The Collaborative Cross, a community resource for the genetic analysis of complex traits
Churchill, G. A., Bogue, M. A., Paigen, B. J., Paigen, K., Pan, H.-J., Svenson, K. L., Airey, D. C., Allayee, H., Angel, J. M., Attie, A., et al. (2004) · Nature Genetics · doi:10.1038/ng1104-1133 · Cited by 1,114 · see citing works
Self-citationTowards the human intestinal microbiota phylogenetic core
Tap, J., Mondot, S., Levenez, F., Pelletier, E., Caron, C., Furet, J., Ugarte, E., Muñoz‐Tamayo, R., Paslier, D. L. E., Nalin, R., et al. (2009) · Environmental Microbiology · doi:10.1111/j.1462-2920.2009.01982.x · Cited by 927 · see citing works
Walter, J., Hertel, C., Tannock, G. W., Lis, C. M., Munro, K., & Hammes, W. P. (2001) · Applied and Environmental Microbiology · doi:10.1128/aem.67.6.2578-2585.2001 · Cited by 782 · see citing works
Self-citationLindgren, C. M., Heid, I. M., Randall, J. C., Lamina, C., Steinthórsdóttir, V., Qi, L., Speliotes, E. K., Þorleifsson, G., Willer, C. J., Herrera, B. M., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000508 · Cited by 701 · see citing works
Hunter, D. J., Peltonen, L., Guiducci, C., Crawford, G., Hirschhorn, J. N., Lyon, H. N., & Speliotes, E. K. (2009) · DSpace@MIT (Massachusetts Institute of Technology) · Cited by 687 · see citing works
Advanced intercross lines, an experimental population for fine genetic mapping.
Darvasi, A., & Soller, M. (1995) · Genetics · doi:10.1093/genetics/141.3.1199 · Cited by 579 · see citing works
STEVENS, C. E., & Hume, I. D. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.2.393 · Cited by 579 · see citing works
The Host Genotype Affects the Bacterial Community in the Human Gastronintestinal Tract
Zoetendal, A. D. L. A. E. G. (2001) · Microbial Ecology in Health and Disease · doi:10.1080/089106001750462669 · Cited by 558 · see citing works
Reproducible Community Dynamics of the Gastrointestinal Microbiota following Antibiotic Perturbation
Antonopoulos, D. A., Huse, S. M., Morrison, H. G., Schmidt, T. M., Sogin, M. L., & Young, V. B. (2009) · Infection and Immunity · doi:10.1128/iai.01520-08 · Cited by 545 · see citing works
de Kimpe, S. J., Kengatharan, M., Thiemermann, C., & Vane, J. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.22.10359 · Cited by 358 · see citing works
Martínez, I., Wallace, G., Zhang, C., Legge, R. M., Benson, A. K., Carr, T. P., Moriyama, E. N., & Walter, J. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.00380-09 · Cited by 355 · see citing works
Self-citationMcFall‐Ngai, M. (2007) · Nature · doi:10.1038/445153a · Cited by 345 · see citing works
THE GASTROINTESTINAL EPITHELIUM AND ITS AUTOCHTHONOUS BACTERIAL FLORA
Savage, D. C., Dubos, R. J., & Schaedler, R. W. (1968) · The Journal of Experimental Medicine · doi:10.1084/jem.127.1.67 · Cited by 333 · see citing works
Predominant Role of Host Genetics in Controlling the Composition of Gut Microbiota
Khachatryan, Z., Ktsoyan, Z. A., Manukyan, G. P., Kelly, D., Ghazaryan, K. A., & Aminov, R. I. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003064 · Cited by 317 · see citing works
A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2
Wang, Q., McLoughlin, R. M., Cobb, B. A., Charrel-Dennis, M., Zaleski, K. J., Golenbock, D. T., Tzianabos, A. O., & Kasper, D. L. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20062008 · Cited by 277 · see citing works
Diversification of the gut symbiont Lactobacillus reuteri as a result of host-driven evolution
Oh, P. L., Benson, A. K., Peterson, D. A., Patil, P. B., Moriyama, E. N., Roos, S., & Walter, J. (2009) · The ISME Journal · doi:10.1038/ismej.2009.123 · Cited by 274 · see citing works
Self-citationChesler, E. J., Miller, D. R., Branstetter, L. R., Galloway, L., Jackson, B. L., Philip, V. M., Voy, B. H., Culiat, C. T., Threadgill, D. W., Williams, R. W., et al. (2008) · Mammalian Genome · doi:10.1007/s00335-008-9135-8 · Cited by 257 · see citing works
van Heel, D. A., Fisher, S. A., Kirby, A., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh090 · Cited by 232 · see citing works
IL-TIF/IL-22: genomic organization and mapping of the human and mouse genes
Dumoutier, L., Roost, E. V., Ameye, G., et al. (2000) · Genes and Immunity · doi:10.1038/sj.gene.6363716 · Cited by 211 · see citing works
Lactobacilli which attach to the crop epithelium of the fowl
Fuller, R., & Brooker, B. E. (1974) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/27.11.1305 · Cited by 151 · see citing works
The Gut Microbiota and Lipid Metabolism: Implications for Human Health and Coronary Heart Disease
Publisher, B. S. P. B. S. (2006) · Current Medicinal Chemistry · doi:10.2174/092986706778521814 · Cited by 131 · see citing works
Alexander, A. D., Orcutt, R. P., Henry, J. C., Baker, J., Bissahoyo, A. C., & Threadgill, D. W. (2006) · Mammalian Genome · doi:10.1007/s00335-006-0063-1 · Cited by 131 · see citing works
Bacteria Associated with Immunoregulatory Cells in Mice
Presley, L. L., Wei, B., Braun, J. G., & Borneman, J. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.01561-09 · Cited by 126 · see citing works
van de Merwe, J. P., Stegeman, J. H., & Hazenberg, M. P. (1983) · Antonie van Leeuwenhoek · doi:10.1007/bf00393669 · Cited by 118 · see citing works
Involvement of IRAK-M in Peptidoglycan-induced Tolerance in Macrophages
Nakayama, K., Okugawa, S., Yanagimoto, S., Kitazawa, T., Tsukada, K., Kawada, M., Kimura, S., Hirai, K., Takagaki, Y., & Ota, Y. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308620200 · Cited by 104 · see citing works
Clavel, T., Charrier, C., Braune, A., Wenning, M., Blaut, M., & Haller, D. (2009) · INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY · doi:10.1099/ijs.0.003087-0 · Cited by 101 · see citing works
Chromosome mapping of murine susceptibility loci to liver carcinogenesis.
Gariboldi, M., Manenti, G., Canzian, F., Falvella, F. S., Pierotti, M. A., Porta, G. D., Binelli, G., & Dragani, T. A. (1993) · PubMed · Cited by 90 · see citing works
What immunologists should know about bacterial communities of the human bowel
Tannock, G. W. (2006) · Seminars in Immunology · doi:10.1016/j.smim.2006.09.001 · Cited by 76 · see citing works
The gastrointestinal microbiome: a malleable, third genome of mammals
Carroll, I. M., Threadgill, D. W., & Threadgill, D. W. (2009) · Mammalian Genome · doi:10.1007/s00335-009-9204-7 · Cited by 66 · see citing works
Comparison of the microbicidal and muramidase activities of mouse lysozyme M and P
Markart, P., Faust, N., Graf, T., et al. (2004) · Biochemical Journal · doi:10.1042/bj20031810 · Cited by 66 · see citing works
Genetic architecture of voluntary exercise in an advanced intercross line of mice
Kelly, S. A., Nehrenberg, D. L., Peirce, J. L., Hua, K., Steffy, B. M., Wiltshire, T., de Villena, F. P., Garland, T., & Pomp, D. (2010) · Physiological Genomics · doi:10.1152/physiolgenomics.00028.2010 · Cited by 63 · see citing works
Self-citationFour new colon cancer susceptibility loci, Scc6 to Scc9 in the mouse.
van Wezel, T., Ruivenkamp, C. A. L., Stassen, A. P. M., et al. (1999) · PubMed · Cited by 52 · see citing works
Bacteria and bacterial rRNA genes associated with the development of colitis in IL-10−/− Mice
Ye, J., Lee, J. W., Presley, L. L., Bent, E., Wei, B., Braun, J. G., Schiller, N. L., Straus, D. S., & Borneman, J. (2008) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20442 · Cited by 51 · see citing works
Quantitative genomics: exploring the genetic architecture of complex trait predisposition.
Pomp, D., Allan, M. F., & Wesolowski, S. R. (2004) · PubMed · doi:10.2527/2004.8213_supple300x · Cited by 40 · see citing works
Self-citationA meta-analysis of QTL for diabetes-related traits in rodents
Schmidt, C., Gonzaludo, N., Strunk, S., Dahm, S., Schuchhardt, J., Kleinjung, F., Wuschke, S., Joost, H., & Al‐Hasani, H. (2008) · Physiological Genomics · doi:10.1152/physiolgenomics.00267.2007 · Cited by 39 · see citing works
Fine mapping of a QTL region with large effects on growth and fatness on mouse chromosome 2
Jerez-Timaure, N., Eisen, E. J., & Pomp, D. (2005) · Physiological Genomics · doi:10.1152/physiolgenomics.00256.2004 · Cited by 37 · see citing works
Self-citationPeirce, J. L., Broman, K. W., Lu, L., Chesler, E. J., Zhou, G., Airey, D. C., Birmingham, A. E., & Williams, R. W. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001977 · Cited by 35 · see citing works
Parent-of-origin effects on voluntary exercise levels and body composition in mice
Kelly, S. A., Nehrenberg, D. L., Hua, K., Gordon, R. R., Garland, T., & Pomp, D. (2009) · Physiological Genomics · doi:10.1152/physiolgenomics.00139.2009 · Cited by 21 · see citing works
Self-citationFarber, C. R., & Medrano, J. F. F. (2007) · Mammalian Genome · doi:10.1007/s00335-007-9046-0 · Cited by 17 · see citing works
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Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Cryan, J. F., & Dinan, T. G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3346 · Cited by 4,572 · see citing works
The impact of the gut microbiota on human health: an integrative view
Clemente, J. C., Ursell, L. K., Parfrey, L. W., & Knight, R. (2012) · Cell · doi:10.1016/j.cell.2012.01.035 · Cited by 3,710 · see citing works
Human Genetics Shape the Gut Microbiome
Goodrich, J. K., Waters, J. L., Poole, A. C., Sutter, J. L., Koren, O., Blekhman, R., Beaumont, M., Van Treuren, W., Knight, R., Bell, J. T., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.053 · Cited by 3,164 · see citing works
Population-level analysis of gut microbiome variation
Falony, G., Joossens, M., Vieira-Silva, S., Wang, J., Darzi, Y., Faust, K., Kurilshikov, A., Bonder, M. J., Valles-Colomer, M., Vandeputte, D., et al. (2016) · Science · doi:10.1126/science.aad3503 · Cited by 2,400 · see citing works
How colonization by microbiota in early life shapes the immune system
Gensollen, T., Iyer, S. S., Kasper, D. L., & Blumberg, R. S. (2016) · Science · doi:10.1126/science.aad9378 · Cited by 2,044 · see citing works
Milani, C., Duranti, S., Bottacini, F., Casey, E., Turroni, F., Mahony, J., Belzer, C., Delgado Palacio, S., Arboleya Montes, S., Mancabelli, L., et al. (2017) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00036-17 · Cited by 1,950 · see citing works
Dysbiosis and the immune system
Levy, M., Kolodziejczyk, A. A., Thaiss, C. A., & Elinav, E. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.7 · Cited by 1,769 · see citing works
Unravelling the effects of the environment and host genotype on the gut microbiome
Spor, A., Koren, O., & Ley, R. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2540 · Cited by 1,509 · see citing works
How informative is the mouse for human gut microbiota research?
Nguyen, T. L. A., Vieira-Silva, S., Liston, A., & Raes, J. (2015) · Disease Models & Mechanisms · doi:10.1242/dmm.017400 · Cited by 1,334 · see citing works
“…founder effects A wide range of experiments in which gene-knockout mouse models have been created, yielding different genetic backgrounds, have highlighted that genetics is an important determinant of gut microbiota composition (Benson et al., 2010; Hildebrand et al., 2013; Kovacs et al., 2011).”
BackgroundIntegrative omics for health and disease
Karczewski, K. J., & Snyder, M. P. (2018) · Nature Reviews Genetics · doi:10.1038/nrg.2018.4 · Cited by 1,158 · see citing works
Diet dominates host genotype in shaping the murine gut microbiota
Carmody, R. N., Gerber, G. K., Luevano, J. M., Gatti, D. M., Somes, L., Svenson, K. L., & Turnbaugh, P. J. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2014.11.010 · Cited by 1,103 · see citing works
Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells
Benakis, C., Brea, D., Caballero, S., Faraco, G., Moore, J., Murphy, M., Sita, G., Racchumi, G., Ling, L., Pamer, E. G., et al. (2016) · Nature Medicine · doi:10.1038/nm.4068 · Cited by 1,114 · see citing works
Genetic determinants of the gut microbiome in UK twins
Goodrich, J. K., Davenport, E. R., Beaumont, M., Jackson, M. A., Knight, R., Ober, C., Spector, T. D., Bell, J. T., Clark, A. G., & Ley, R. E. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.04.017 · Cited by 1,048 · see citing works
Bennett, B. J., Vallim, T. Q. D. A., Wang, Z., Shih, D. M., Meng, Y., Gregory, J., Allayee, H., Lee, R., Graham, M., Crooke, R., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.011 · Cited by 1,070 · see citing works
Bäckhed, F., Fraser, C. M., Ringel, Y., Sanders, M. E., Sartor, R. B., Sherman, P. M., Versalovic, J., Young, V., & Finlay, B. B. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.10.012 · Cited by 836 · see citing works
Microbiota and Host Nutrition across Plant and Animal Kingdoms
Hacquard, S., Garrido-Oter, R., González, A., Spaepen, S., Ackermann, G., Lebeis, S., McHardy, A. C., Dangl, J. L., Knight, R., Ley, R., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.009 · Cited by 779 · see citing works
The human microbiome: Our second genome
Grice, E. A., & Segre, J. A. (2012) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090711-163814 · Cited by 759 · see citing works
Plottel, C. S., & Blaser, M. J. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.10.003 · Cited by 743 · see citing works
The human gut microbiome: ecology and recent evolutionary changes
Walter, J., & Ley, R. (2011) · Annual Review of Microbiology · doi:10.1146/annurev-micro-090110-102830 · Cited by 720 · see citing works
Self-citationGoodrich, J. K., Di Rienzi, S. C., Poole, A. C., Koren, O., Walters, W. A., Caporaso, J. G., Knight, R., & Ley, R. E. (2014) · Cell · doi:10.1016/j.cell.2014.06.037 · Cited by 714 · see citing works
Wang, J., Thingholm, L. B., Skiecevičienė, J., Rausch, P., Kummen, M., Hov, J. R., Degenhardt, F., Heinsen, F.-A., Rühlemann, M. C., Szymczak, S., et al. (2016) · Nature Genetics · doi:10.1038/ng.3695 · Cited by 625 · see citing works
Verdam, F. J., Fuentes, S., de Jonge, C., Zoetendal, E. G., Erbil, R., Greve, J. W., Buurman, W. A., de Vos, W. M., & Rensen, S. S. (2013) · Obesity · doi:10.1002/oby.20466 · Cited by 587 · see citing works
Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock
Liang, X., Bushman, F. D., & FitzGerald, G. A. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1501305112 · Cited by 578 · see citing works
Biesbroek, G., Tsivtsivadze, E., Sanders, E. A. M., Montijn, R., Veenhoven, R. H., Keijser, B. J. F., & Bogaert, D. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201407-1240oc · Cited by 572 · see citing works
Parks, B. W., Nam, E., Org, E., Kostem, E., Norheim, F., Hui, S. T., Pan, C., Civelek, M., Rau, C. D., Bennett, B. J., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.007 · Cited by 544 · see citing works
Li, F., Li, C., Chen, Y., Liu, J., Zhang, C., Irving, B., Fitzsimmons, C., Plastow, G., & Guan, L. L. (2019) · Microbiome · doi:10.1186/s40168-019-0699-1 · Cited by 530 · see citing works
Dietary effects on human gut microbiome diversity
Xu, Z., & Knight, R. (2015) · British Journal Of Nutrition · doi:10.1017/s0007114514004127 · Cited by 456 · see citing works
Metagenome-wide association studies: fine-mining the microbiome
Wang, J., & Jia, H. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.83 · Cited by 429 · see citing works
Development of the human gastrointestinal microbiota and insights from high-throughput sequencing
Dominguez-Bello, M. G., Blaser, M. J., Ley, R. E., & Knight, R. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.02.011 · Cited by 405 · see citing works
Microbiota conservation and BMI signatures in adult monozygotic twins
Tims, S., Derom, C., Jonkers, D. M., Vlietinck, R., Saris, W. H., Kleerebezem, M., de Vos, W. M., & Zoetendal, E. G. (2013) · The ISME Journal · doi:10.1038/ismej.2012.146 · Cited by 367 · see citing works
Genetic and environmental control of host-gut microbiota interactions
Org, E., Parks, B. W., Joo, J. W. J., Emert, B., Schwartzman, W., Kang, E. Y., Mehrabian, M., Pan, C., Knight, R., Gunsalus, R., et al. (2015) · Genome Research · doi:10.1101/gr.194118.115 · Cited by 381 · see citing works
Microbiomes as sources of emergent host phenotypes
Lynch, J. B., & Hsiao, E. Y. (2019) · Science · doi:10.1126/science.aay0240 · Cited by 339 · see citing works
Roehe, R., Dewhurst, R. J., Duthie, C.-A., Rooke, J. A., McKain, N., Ross, D. W., Hyslop, J. J., Waterhouse, A., Freeman, T. C., Watson, M., et al. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005846 · Cited by 359 · see citing works
Xie, H., Guo, R., Zhong, H., Feng, Q., Lan, Z., Qin, B., Ward, K. J., Jackson, M. A., Xia, Y., Chen, X., et al. (2016) · Cell Systems · doi:10.1016/j.cels.2016.10.004 · Cited by 341 · see citing works
Serum level of sex steroid hormone is associated with diversity and profiles of human gut microbiome
Shin, J.-H., Park, Y.-H., Sim, M., Kim, S.-A., Joung, H., & Shin, D.-M. (2019) · Research in Microbiology · doi:10.1016/j.resmic.2019.03.003 · Cited by 334 · see citing works
Gut Microbiota, Intestinal Permeability, Obesity‐Induced Inflammation, and Liver Injury
Frazier, T. H., DiBaise, J. K., & McClain, C. J. (2011) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607111413772 · Cited by 306 · see citing works
Host Genetics and Gut Microbiome: Challenges and Perspectives
Kurilshikov, A., Wijmenga, C., Fu, J., & Zhernakova, A. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.06.003 · Cited by 309 · see citing works
Microbiota regulation of the mammalian gut-brain axis
Burokas, A., Moloney, R. D., Dinan, T. G., & Cryan, J. F. (2015) · Advances in applied microbiology · doi:10.1016/bs.aambs.2015.02.001 · Cited by 300 · see citing works
Irritable bowel syndrome: a gut microbiota-related disorder?
Bhattarai, Y., Muniz Pedrogo, D. A., & Kashyap, P. C. (2017) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00338.2016 · Cited by 294 · see citing works
Microbes, immunity, and behavior: psychoneuroimmunology meets the microbiome
Dinan, T. G., & Cryan, J. F. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.103 · Cited by 246 · see citing works
Emerging roles of the microbiome in cancer
Bultman, S. J. (2014) · Carcinogenesis · doi:10.1093/carcin/bgt392 · Cited by 239 · see citing works
Bile acids drive the newborn’s gut microbiota maturation
van Best, N., Rolle-Kampczyk, U., Schaap, F. G., Basic, M., Olde Damink, S. W. M., Bleich, A., Savelkoul, P. H. M., von Bergen, M., Penders, J., & Hornef, M. W. (2020) · Nature Communications · doi:10.1038/s41467-020-17183-8 · Cited by 226 · see citing works
The influence of the gut microbiome on obesity, metabolic syndrome and gastrointestinal disease
Parekh, P. J., Balart, L. A., & Johnson, D. A. (2015) · Clinical and Translational Gastroenterology · doi:10.1038/ctg.2015.16 · Cited by 219 · see citing works
Sasson, G., Kruger Ben-Shabat, S., Seroussi, E., Doron-Faigenboim, A., Shterzer, N., Yaacoby, S., Berg Miller, M. E., White, B. A., Halperin, E., & Mizrahi, I. (2017) · mBio · doi:10.1128/mbio.00703-17 · Cited by 219 · see citing works
Chen, J., & Li, H. (2013) · The Annals of Applied Statistics · doi:10.1214/12-aoas592 · Cited by 191 · see citing works
“Benson et al. (2010) demonstrated that genetic variants are associated with the mouse gut microbiome.”
The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse
Morgan, A. P., Crowley, J. J., Nonneman, R. J., Quackenbush, C. R., Miller, C. N., Ryan, A. K., Bogue, M. A., Paredes, S. H., Yourstone, S., Carroll, I. M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115225 · Cited by 197 · see citing works
Host genetic variation and its microbiome interactions within the Human Microbiome Project
Kolde, R., Franzosa, E. A., Rahnavard, G., Hall, A. B., Vlamakis, H., Stevens, C., Daly, M. J., Xavier, R. J., & Huttenhower, C. (2018) · Genome Medicine · doi:10.1186/s13073-018-0515-8 · Cited by 182 · see citing works
Martínez, I., Maldonado-Gomez, M. X., Gomes-Neto, J. C., Kittana, H., Ding, H., Schmaltz, R., Joglekar, P., Cardona, R. J., Marsteller, N. L., Kembel, S. W., et al. (2018) · eLife · doi:10.7554/elife.36521 · Cited by 199 · see citing works
Self-citationMalnutrition in Obesity: Is It Possible?
Kobylińska, M., Antosik, K., Decyk, A., & Kurowska, K. (2022) · Obesity Facts · doi:10.1159/000519503 · Cited by 186 · see citing works
From pre- to postweaning: transformation of the young calf's gastrointestinal tract
Meale, S. J., Chaucheyras-Durand, F., Berends, H., Guan, L. L., & Steele, M. A. (2017) · Journal of Dairy Science · doi:10.3168/jds.2016-12474 · Cited by 163 · 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 microbiota changes in children with autism spectrum disorder: a systematic review
Ho, L. K. H., Tong, V. J. W., Syn, N., Nagarajan, N., Tham, E. H., Tay, S. K., Shorey, S., Tambyah, P. A., & Law, E. C. N. (2020) · Gut Pathogens · doi:10.1186/s13099-020-0346-1 · Cited by 149 · see citing works
Yan, H., Diao, H., Xiao, Y., Li, W., Yu, B., He, J., Yu, J., Zheng, P., Mao, X., Luo, Y., et al. (2016) · Scientific Reports · doi:10.1038/srep31786 · Cited by 138 · see citing works
Soy and Gut Microbiota: Interaction and Implication for Human Health
Huang, H., Krishnan, H. B., Pham, Q., Yu, L. L., & Wang, T. T. Y. (2016) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6b03725 · Cited by 138 · see citing works
Early Development of the Gut Microbiome and Immune-Mediated Childhood Disorders
Li, M., Wang, M., & Donovan, S. (2014) · Seminars in Reproductive Medicine · doi:10.1055/s-0033-1361825 · Cited by 131 · see citing works
Hughes, R. L., Kable, M. E., Marco, M., & Keim, N. L. (2019) · Advances in Nutrition · doi:10.1093/advances/nmz049 · Cited by 117 · see citing works
Ikeda-Ohtsubo, W., Brugman, S., Warden, C. H., Rebel, J. M. J., Folkerts, G., & Pieterse, C. M. J. (2018) · Frontiers in Nutrition · doi:10.3389/fnut.2018.00090 · Cited by 115 · see citing works
Hygiene and other early childhood influences on the subsequent function of the immune system
Rook, G. A. W., Lowry, C. A., & Raison, C. L. (2015) · Brain Research · doi:10.1016/j.brainres.2014.04.004 · Cited by 109 · see citing works
Gut microbiota regulates key modulators of social behavior
Parashar, A., & Udayabanu, M. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.11.002 · Cited by 88 · see citing works
Commensal gut flora and brain autoimmunity: a love or hate affair?
Berer, K., & Krishnamoorthy, G. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0949-9 · Cited by 82 · see citing works
Ringel-Kulka, T., Benson, A. K., Carroll, I. M., Kim, J., Legge, R. M., & Ringel, Y. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00044.2015 · Cited by 53 · see citing works
Self-citationGenetic modification of iron metabolism in mice affects the gut microbiota
Buhnik-Rosenblau, K., Moshe-Belizowski, S., Danin-Poleg, Y., & Meyron-Holtz, E. G. (2012) · BioMetals · doi:10.1007/s10534-012-9555-5 · Cited by 53 · see citing works
Brito, L. F., Oliveira, H. R., Houlahan, K., Fonseca, P. A. S., Lam, S., Butty, A. M., Seymour, D. J., Vargas, G., Chud, T. C. S., Silva, F. F., et al. (2020) · Canadian Journal of Animal Science · doi:10.1139/cjas-2019-0193 · Cited by 53 · see citing works
Zhang, Q., Linke, V., Overmyer, K. A., Traeger, L. L., Kasahara, K., Miller, I. J., Manson, D. E., Polaske, T. J., Kerby, R. L., Kemis, J. H., et al. (2023) · Nature Microbiology · doi:10.1038/s41564-023-01326-w · Cited by 43 · see citing works
Gut microbiota imbalance and base excision repair dynamics in colon cancer
Ray, D., & Kidane, D. (2016) · Journal of Cancer · doi:10.7150/jca.15480 · Cited by 37 · see citing works
Sun, F., & Xu, Z. (2021) · Journal of Marine Science and Engineering · doi:10.3390/jmse9020104 · Cited by 35 · see citing works
Golder, H. M., Thomson, J. M., Denman, S. E., McSweeney, C. S., & Lean, I. J. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00062 · Cited by 32 · see citing works
Casaro, M. B., Thomas, A. M., Mendes, E., Fukumori, C., Ribeiro, W. R., Oliveira, F. A., Crisma, A. R., Murata, G. M., Bizzarro, B., Sá-Nunes, A., et al. (2021) · Microbiome · doi:10.1186/s40168-021-01081-2 · Cited by 24 · see citing works
Pekkala, S., Lensu, S., Nokia, M., Vanhatalo, S., Koch, L. G., Britton, S. L., & Kainulainen, H. (2017) · Physiological Genomics · doi:10.1152/physiolgenomics.00081.2017 · Cited by 16 · see citing works
The road not taken: host genetics in shaping intergenerational microbiomes
Zeng, S., Wang, S., Ross, R. P., & Stanton, C. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.05.016 · Cited by 9 · see citing works
Wang, H.-X., & Wang, Y.-P. (2016) · Chinese Medical Journal · doi:10.4103/0366-6999.190667 · Cited by 546 · see citing works
- Authors
- Benson, A. K., Kelly, S. A., Legge, R., Ma, F., Low, S. J., Kim, J., Zhang, M., Oh, P. L., Nehrenberg, D., Hua, K., Kachman, S. D., Moriyama, E. N., Walter, J., Peterson, D. A., & Pomp, D.
- Affiliations
- University of Nebraska–Lincoln (US)
- University of North Carolina at Chapel Hill (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-10-11
- Volume
- 107
- Issue
- 44
- Pages
- 18933-18938
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2973891
- OpenAlex
- W2092696502
- Cited by
- 1,314
- References
- 58
- Citations by year
- 2026: 36 · 2025: 53 · 2024: 68 · 2023: 82 · 2022: 89 · 2021: 116 · 2020: 99 · 2019: 110 · 2018: 80 · 2017: 98 · 2016: 117 · 2015: 90 · 2014: 89 · 2013: 71 · 2012: 67
- FWCI
- 24.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- UNC Libraries
- Funders
- North Carolina State University
- Michigan State University
- University of Nebraska-Lincoln
- College of Engineering, Michigan State University
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-076050, RC1DK087346, R01DK076050, DK-056350, P30DK056350)
- National Institute of Environmental Health Sciences (P30ES010126)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- gut microbiota, host genetics, quantitative trait loci, polygenic traits, C57BL/6J mice, microbial community composition, pleiotropy, host-microbe interactions, environmental factors
- MeSH terms
- Animals, Bacteria, Breeding, Humans, Intestines, Genetic Linkage, Mice, Inbred ICR, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Mice, Host-Pathogen Interactions, Genome-Wide Association Study
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