Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Disentangling host–microbiota complexity through hologenomics

Abstract

Research on animal–microbiota interactions has become a central topic in biological sciences because of its relevance to basic eco-evolutionary processes and applied questions in agriculture and health. However, animal hosts and their associated microbial communities are still seldom studied in a systemic fashion. Hologenomics, the integrated study of the genetic features of a eukaryotic host alongside that of its associated microbes, is becoming a feasible — yet still underexploited — approach that overcomes this limitation. Acknowledging the biological and genetic properties of both hosts and microbes, along with the advantages and disadvantages of implemented techniques, is essential for designing optimal studies that enable some of the major questions in biology to be addressed.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Diversity and ecological relevance of host–microbiota systems.
Fig. 2: Overview of the five essential criteria for designing and interpreting hologenomic studies.
Fig. 3: Decomposition of hologenomic complexity.
Fig. 4: Hologenomic complexity of study systems.
Fig. 5: Examples of biological processes addressed by the different models of host–microbiota interactions.
Fig. 6: Decomposition of hologenomic complexity and its impact on results.

References

  1. 1.

    McFall-Ngai, M. et al. Animals in a bacterial world, a new imperative for the life sciences. Proc. Natl Acad. Sci. USA 110, 3229–3236 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Bosch, T. C. G. & Miller, D. J. The Holobiont Imperative: Perspective from Early Emerging Animals (Springer-Verlag, 2016).

  3. 3.

    Müller, D. B., Vogel, C., Bai, Y. & Vorholt, J. A. The plant microbiota: systems-level insights and perspectives. Annu. Rev. Genet. 50, 211–234 (2016).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  4. 4.

    Baedke, J., Fábregas-Tejeda, A. & Nieves Delgado, A. The holobiont concept before Margulis. J. Exp. Zool. B Mol. Dev. Evol. 334, 149–155 (2020).

    PubMed  Article  PubMed Central  Google Scholar 

  5. 5.

    Nyholm, S. V. & McFall-Ngai, M. The winnowing: establishing the squid–vibrio symbiosis. Nat. Rev. Microbiol. 2, 632–642 (2004).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  6. 6.

    Ley, R. E., Lozupone, C. A., Hamady, M., Knight, R. & Gordon, J. I. Worlds within worlds: evolution of the vertebrate gut microbiota. Nat. Rev. Microbiol. 6, 776–788 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Sasse, J., Martinoia, E. & Northen, T. Feed your friends: do plant exudates shape the root microbiome? Trends Plant. Sci. 23, 25–41 (2018).

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Małyska, A., Markakis, M. N., Pereira, C. F. & Cornelissen, M. The microbiome: a life science opportunity for our society and our planet. Trends Biotechnol. 37, 1269–1272 (2019).

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Sessitsch, A. & Mitter, B. 21st century agriculture: integration of plant microbiomes for improved crop production and food security. Microb. Biotechnol. 8, 32 (2015).

    PubMed  Article  Google Scholar 

  10. 10.

    Leidy, J. Parasites of the Termites (Collins, Printer, 1881).

  11. 11.

    Escherich, T. The intestinal bacteria of the neonate and breast-fed infant. Rev. Infect. Dis. 10, 1220–1225 (1988).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  12. 12.

    Beckwith, T. D. & Rose, E. J. Cellulose digestion by organisms from the termite gut. Proc. Soc. Exp. Biol. Med. 27, 4–6 (1929).

    CAS  Article  Google Scholar 

  13. 13.

    Margolin, S. Methods for the cultivation of cattle ciliates. Biol. Bull. 59, 301–305 (1930).

    Article  Google Scholar 

  14. 14.

    Bergeim, O., Hanszen, A. & Arnold, L. The influence of fruit ingestion before meals upon the bacterial flora of stomach and large intestine and on food allergins. Am. J. Dig. Dis. Nutr. 3, 45–52 (1936).

    CAS  Article  Google Scholar 

  15. 15.

    Lewin, H. A. et al. Earth BioGenome Project: sequencing life for the future of life. Proc. Natl Acad. Sci. USA 115, 4325–4333 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Quince, C., Walker, A. W., Simpson, J. T., Loman, N. J. & Segata, N. Shotgun metagenomics, from sampling to analysis. Nat. Biotechnol. 35, 833–844 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  17. 17.

    Jefferson, R. The Hologenome. Agriculture, Environment and the Developing World: A Future of PCR (Cold Spring Harbor Press, 1994).

  18. 18.

    Nyholm, L. et al. Holo-omics: integrated host-microbiota multi-omics for basic and applied biological research. iScience 23, 101414 (2020). This article provides an overview of possible applications of hologenomics across basic and applied biological sciences.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Limborg, M. T. et al. Applied hologenomics: feasibility and potential in aquaculture. Trends Biotechnol. 36, 252–264 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  20. 20.

    Zepeda Mendoza, M. L. et al. Hologenomic adaptations underlying the evolution of sanguivory in the common vampire bat. Nat. Ecol. Evol. 2, 659–668 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  21. 21.

    Foster, K. R., Schluter, J., Coyte, K. Z. & Rakoff-Nahoum, S. The evolution of the host microbiome as an ecosystem on a leash. Nature 548, 43–51 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Theis, K. R. et al. Getting the hologenome concept right: an eco-evolutionary framework for hosts and their microbiomes. mSystems 1, e00028-16 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Moran, N. A. & Sloan, D. B. The hologenome concept: helpful or hollow? PLoS Biol. 13, e1002311 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  24. 24.

    Lloyd, E. A. & Wade, M. J. Criteria for holobionts from community genetics. Biol. Theory 14, 151–170 (2019).

    Article  Google Scholar 

  25. 25.

    Srinivas, G. et al. Genome-wide mapping of gene–microbiota interactions in susceptibility to autoimmune skin blistering. Nat. Commun. 4, 2462 (2013).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  26. 26.

    Bashiardes, S., Godneva, A., Elinav, E. & Segal, E. Towards utilization of the human genome and microbiome for personalized nutrition. Curr. Opin. Biotechnol. 51, 57–63 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  27. 27.

    Bermudez-Brito, M., Plaza-Díaz, J., Fontana, L., Muñoz-Quezada, S. & Gil, A. In vitro cell and tissue models for studying host–microbe interactions: a review. Br. J. Nutr. 109, S27–S34 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  28. 28.

    Hasin, Y., Seldin, M. & Lusis, A. Multi-omics approaches to disease. Genome Biol. 18, 83 (2017).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  29. 29.

    Argelaguet, R. et al. Multi-Omics Factor Analysis — a framework for unsupervised integration of multi-omics data sets. Mol. Syst. Biol. 14, e8124 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  30. 30.

    Singh, A. et al. DIABLO: an integrative approach for identifying key molecular drivers from multi-omics assays. Bioinformatics 35, 3055–3062 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Almeida, A. et al. A unified catalog of 204,938 reference genomes from the human gut microbiome. Nat. Biotechnol. 39, 105–114 (2021).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  32. 32.

    Xu, L. et al. Holo-omics for deciphering plant-microbiome interactions. Microbiome 9, 69 (2021).

    PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Lynch, M. & Walsh, B. The Origins of Genome Architecture. Vol. 98 (Sinauer Associates, 2007).

  34. 34.

    Donoghue, P. C. J. & Purnell, M. A. Genome duplication, extinction and vertebrate evolution. Trends Ecol. Evol. 20, 312–319 (2005).

    PubMed  Article  PubMed Central  Google Scholar 

  35. 35.

    De Bodt, S., Maere, S. & Van de Peer, Y. Genome duplication and the origin of angiosperms. Trends Ecol. Evol. 20, 591–597 (2005).

    PubMed  Article  PubMed Central  Google Scholar 

  36. 36.

    Liedtke, H. C., Gower, D. J., Wilkinson, M. & Gomez-Mestre, I. Macroevolutionary shift in the size of amphibian genomes and the role of life history and climate. Nat. Ecol. Evol. 2, 1792–1799 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  37. 37.

    Comai, L. The advantages and disadvantages of being polyploid. Nat. Rev. Genet. 6, 836–846 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  38. 38.

    Goodrich, J. K. et al. Human genetics shape the gut microbiome. Cell 159, 789–799 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. 39.

    Turnbaugh, P. J., Bäckhed, F., Fulton, L. & Gordon, J. I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3, 213–223 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. 40.

    Peiffer, J. A. et al. Diversity and heritability of the maize rhizosphere microbiome under field conditions. Proc. Natl Acad. Sci. USA 110, 6548–6553 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  41. 41.

    Fietz, K. et al. Mind the gut: genomic insights to population divergence and gut microbial composition of two marine keystone species. Microbiome 6, 82 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  42. 42.

    Ofek-Lalzar, M. et al. Niche and host-associated functional signatures of the root surface microbiome. Nat. Commun. 5, 4950 (2014).

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Sumigray, K. D., Terwilliger, M. & Lechler, T. Morphogenesis and compartmentalization of the intestinal crypt. Dev. Cell 45, 183–197.e5 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. 44.

    Pabst, O. & Slack, E. IgA and the intestinal microbiota: the importance of being specific. Mucosal Immunol. 13, 12–21 (2020).

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    Bolnick, D. I. et al. Individual diet has sex-dependent effects on vertebrate gut microbiota. Nat. Commun. 5, 4500 (2014).

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Karp, N. A. et al. Prevalence of sexual dimorphism in mammalian phenotypic traits. Nat. Commun. 8, 15475 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. 47.

    Dahlman, S., Avellaneda-Franco, L. & Barr, J. J. Phages to shape the gut microbiota? Curr. Opin. Biotechnol. 68, 89–95 (2020).

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Edwards, J. A. et al. Compositional shifts in root-associated bacterial and archaeal microbiota track the plant life cycle in field-grown rice. PLoS Biol. 16, e2003862 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  49. 49.

    Danczak, R. E. et al. Members of the candidate phyla radiation are functionally differentiated by carbon- and nitrogen-cycling capabilities. Microbiome 5, 112 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. 50.

    Siriyappagouder, P. et al. Exposure to yeast shapes the intestinal bacterial community assembly in zebrafish larvae. Front. Microbiol. 9, 1868 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  51. 51.

    Chabé, M., Lokmer, A. & Ségurel, L. Gut protozoa: friends or foes of the human gut microbiota? Trends Parasitol. 33, 925–934 (2017).

    PubMed  Article  Google Scholar 

  52. 52.

    Leung, J. M., Graham, A. L. & Knowles, S. C. L. Parasite-microbiota interactions with the vertebrate gut: synthesis through an ecological lens. Front. Microbiol. 9, 843 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Moya, A. & Ferrer, M. Functional redundancy-induced stability of gut microbiota subjected to disturbance. Trends Microbiol. 24, 402–413 (2016).

    CAS  PubMed  Article  Google Scholar 

  54. 54.

    Stanton-Geddes, J. et al. Thermal reactionomes reveal divergent responses to thermal extremes in warm and cool-climate ant species. BMC Genomics 17, 171 (2016).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  55. 55.

    Megha, S., Basu, U. & Kav, N. N. V. Regulation of low temperature stress in plants by microRNAs. Plant. Cell Env. 41, 1–15 (2018).

    CAS  Article  Google Scholar 

  56. 56.

    Yu, T. & Chen, Y. Effects of elevated carbon dioxide on environmental microbes and its mechanisms: a review. Sci. Total. Environ. 655, 865–879 (2019).

    CAS  PubMed  Article  Google Scholar 

  57. 57.

    Mushegian, A. A., Arbore, R., Walser, J.-C. & Ebert, D. Environmental sources of bacteria and genetic variation in behavior influence host-associated microbiota. Appl. Environ. Microbiol. 85, e01547–18 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  58. 58.

    Vannier, N. et al. A microorganisms’ journey between plant generations. Microbiome 6, 79 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  59. 59.

    Sommer, F. et al. The gut microbiota modulates energy metabolism in the hibernating brown bear ursus arctos. Cell Rep. 14, 1655–1661 (2016).

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Fung, T. C. et al. Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut. Nat. Microbiol. 4, 2064–2073 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  61. 61.

    Li, Y. et al. Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5−/− mice. Nat. Commun. 10, 1492 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  62. 62.

    Bein, A. et al. Microfluidic organ-on-a-chip models of human intestine. Cell Mol. Gastroenterol. Hepatol. 5, 659–668 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  63. 63.

    Knowles, S. C. L., Eccles, R. M. & Baltrūnaitė, L. Species identity dominates over environment in shaping the microbiota of small mammals. Ecol. Lett. 22, 826–837 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  64. 64.

    Brito, I. L. et al. Transmission of human-associated microbiota along family and social networks. Nat. Microbiol. 4, 964–971 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  65. 65.

    Michalak, L. et al. Microbiota-directed fibre activates both targeted and secondary metabolic shifts in the distal gut. Nat. Commun. 11, 5773 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. 66.

    Muller, P. A. et al. Microbiota modulate sympathetic neurons via a gut–brain circuit. Nature 583, 441–446 (2020). This paper shows that the microbiota modulates the expression of the neuronal transcription factor cFos through SCFAs in the gut sympathetic ganglia.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. 67.

    Khoruts, A. & Sadowsky, M. J. Understanding the mechanisms of faecal microbiota transplantation. Nat. Rev. Gastroenterol. Hepatol. 13, 508–516 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  68. 68.

    Bojanova, D. P. & Bordenstein, S. R. Fecal transplants: what is being transferred? PLoS Biol. 14, e1002503 (2016).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  69. 69.

    Rasmussen, T. S. et al. Bacteriophage-mediated manipulation of the gut microbiome - promises and presents limitations. FEMS Microbiol. Rev. 44, 507–521 (2020).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  70. 70.

    Vázquez-Castellanos, J. F., Biclot, A., Vrancken, G., Huys, G. R. B. & Raes, J. Design of synthetic microbial consortia for gut microbiota modulation. Curr. Opin. Pharmacol. 49, 52–59 (2019).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  71. 71.

    Kehe, J. et al. Massively parallel screening of synthetic microbial communities. Proc. Natl Acad. Sci. USA 116, 12804–12809 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  72. 72.

    Kim, H. J., Li, H., Collins, J. J. & Ingber, D. E. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. Proc. Natl Acad. Sci. USA 113, E7–E15 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  73. 73.

    D’hoe, K. et al. Integrated culturing, modeling and transcriptomics uncovers complex interactions and emergent behavior in a three-species synthetic gut community. Elife 8, e37090 (2018).

    Article  Google Scholar 

  74. 74.

    Lawson, C. E. et al. Common principles and best practices for engineering microbiomes. Nat. Rev. Microbiol. 17, 725–741 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  75. 75.

    Mimee, M. et al. An ingestible bacterial-electronic system to monitor gastrointestinal health. Science 360, 915–918 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  76. 76.

    Riglar, D. T. & Silver, P. A. Engineering bacteria for diagnostic and therapeutic applications. Nat. Rev. Microbiol. 16, 214–225 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  77. 77.

    McCarty, N. S. & Ledesma-Amaro, R. Synthetic biology tools to engineer microbial communities for biotechnology. Trends Biotechnol. 37, 181–197 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. 78.

    Ruiz-Rodríguez, M., Martín-Vivaldi, M., Martínez-Bueno, M. & Soler, J. J. Gut microbiota of great spotted cuckoo nestlings is a mixture of those of their foster magpie siblings and of cuckoo adults. Genes 9, 381 (2018).

    PubMed Central  Article  CAS  Google Scholar 

  79. 79.

    Taylor, R. S. & Friesen, V. L. The role of allochrony in speciation. Mol. Ecol. 26, 3330–3342 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  80. 80.

    Wang, Q. et al. Host and microbiome multi-omics integration: applications and methodologies. Biophys. Rev. 11, 55–65 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. 81.

    Nielsen, R. L. et al. Data integration for prediction of weight loss in randomized controlled dietary trials. Sci. Rep. 10, 20103 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. 82.

    Sankaran, K. & Holmes, S. P. Multitable methods for microbiome data integration. Front. Genet. 10, 627 (2019).

    PubMed  PubMed Central  Article  Google Scholar 

  83. 83.

    Frankel-Bricker, J., Song, M. J., Benner, M. J. & Schaack, S. Variation in the microbiota associated with Daphnia magna across genotypes, populations, and temperature. Microb. Ecol. 79, 731–742 (2020).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  84. 84.

    Dirksen, P. et al. The native microbiome of the nematode Caenorhabditis elegans: gateway to a new host-microbiome model. BMC Biol. 14, 38 (2016).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  85. 85.

    Org, E. et al. Genetic and environmental control of host-gut microbiota interactions. Genome Res. 25, 1558–1569 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  86. 86.

    Suzuki, T. A. et al. Host genetic determinants of the gut microbiota of wild mice. Mol. Ecol. 28, 3197–3207 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  87. 87.

    Groussin, M. et al. Unraveling the processes shaping mammalian gut microbiomes over evolutionary time. Nat. Commun. 8, 14319 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  88. 88.

    Chiang, C. et al. The impact of structural variation on human gene expression. Nat. Genet. 49, 692–699 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  89. 89.

    Ansari, I. et al. The microbiota programs DNA methylation to control intestinal homeostasis and inflammation. Nat. Microbiol. 5, 610–619 (2020). This article demonstrates that intestinal microorganisms induce epigenetic changes in regulatory features of host genes.

    CAS  PubMed  Article  Google Scholar 

  90. 90.

    Woo, V. & Alenghat, T. Host-microbiota interactions: epigenomic regulation. Curr. Opin. Immunol. 44, 52–60 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  91. 91.

    Lieberman-Aiden, E. et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326, 289–293 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  92. 92.

    Awany, D. et al. Host and microbiome genome-wide association studies: current state and challenges. Front. Genet. 9, 637 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  93. 93.

    Callahan, B. J., McMurdie, P. J. & Holmes, S. P. Exact sequence variants should replace operational taxonomic units in marker-gene data analysis. ISME J. 11, 2639–2643 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  94. 94.

    Johnson, J. S. et al. Evaluation of 16S rRNA gene sequencing for species and strain-level microbiome analysis. Nat. Commun. 10, 5029 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  95. 95.

    Goyal, A., Bittleston, L. S., Leventhal, G. E., Lu, L. & Cordero, O. X. Interactions between strains govern the eco-evolutionary dynamics of microbial communities. bioRxiv https://doi.org/10.1101/2021.01.04.425224 (2021).

    Article  Google Scholar 

  96. 96.

    Antony-Babu, S. et al. Multiple Streptomyces species with distinct secondary metabolomes have identical 16S rRNA gene sequences. Sci. Rep. 7, 11089 (2017).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  97. 97.

    Aßhauer, K. P., Wemheuer, B., Daniel, R. & Meinicke, P. Tax4Fun: predicting functional profiles from metagenomic 16S rRNA data. Bioinformatics 31, 2882–2884 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  98. 98.

    Iwai, S. et al. Piphillin: improved prediction of metagenomic content by direct inference from human microbiomes. PLoS One 11, e0166104 (2016).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  99. 99.

    Langille, M. G. I. et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat. Biotechnol. 31, 814–821 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  100. 100.

    Sun, S., Jones, R. B. & Fodor, A. A. Inference-based accuracy of metagenome prediction tools varies across sample types and functional categories. Microbiome 8, 46 (2020).

    PubMed  PubMed Central  Article  Google Scholar 

  101. 101.

    Lesker, T. R. et al. An integrated metagenome catalog reveals new insights into the murine gut microbiome. Cell Rep. 30, 2909–2922.e6 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  102. 102.

    Nayfach, S. et al. A genomic catalog of Earth’s microbiomes. Nat. Biotechnol. 39, 499–509 (2021).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  103. 103.

    Overholt, W. A. et al. Inclusion of Oxford Nanopore long reads improves all microbial and viral metagenome-assembled genomes from a complex aquifer system. Environ. Microbiol. 22, 4000–4013 (2020).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  104. 104.

    Jiang, Y., Balaban, M., Zhu, Q. & Mirarab, S. DEPP: deep learning enables extending species trees using single genes. bioRxiv https://doi.org/10.1101/2021.01.22.427808 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  105. 105.

    Zhao, L. et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 359, 1151–1156 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  106. 106.

    Minot, S. S. & Willis, A. D. Clustering co-abundant genes identifies components of the gut microbiome that are reproducibly associated with colorectal cancer and inflammatory bowel disease. Microbiome 7, 110 (2019).

    PubMed  PubMed Central  Article  Google Scholar 

  107. 107.

    Martino, C. et al. Context-aware dimensionality reduction deconvolutes gut microbial community dynamics. Nat. Biotechnol. 39, 165–168 (2021).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  108. 108.

    Xu, Y. Envirotyping for deciphering environmental impacts on crop plants. Theor. Appl. Genet. 129, 653–673 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  109. 109.

    Foote, A. D. et al. Genome-culture coevolution promotes rapid divergence of killer whale ecotypes. Nat. Commun. 7, 11693 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  110. 110.

    Rojas, C. A., Holekamp, K. E., Winters, A. D. & Theis, K. R. Body site-specific microbiota reflect sex and age-class among wild spotted hyenas. FEMS Microbiol. Ecol. 96, fiaa007 (2020).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  111. 111.

    Riva, A. et al. A fiber-deprived diet disturbs the fine-scale spatial architecture of the murine colon microbiome. Nat. Commun. 10, 4366 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  112. 112.

    Sheth, R. U. et al. Spatial metagenomic characterization of microbial biogeography in the gut. Nat. Biotechnol. 37, 877–883 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  113. 113.

    Zaborin, A. et al. Spatial compartmentalization of the microbiome between the lumen and crypts is lost in the murine cecum following the process of surgery, including overnight fasting and exposure to antibiotics. mSystems 5, e00377 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  114. 114.

    Ellegaard, K. M. & Engel, P. Genomic diversity landscape of the honey bee gut microbiota. Nat. Commun. 10, 446 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  115. 115.

    Shah, T. M., Patel, J. G., Gohil, T. P., Blake, D. P. & Joshi, C. G. Host transcriptome and microbiome interaction modulates physiology of full-sibs broilers with divergent feed conversion ratio. NPJ Biofilms Microb. 5, 24 (2019).

    Article  CAS  Google Scholar 

  116. 116.

    Fukami, T. Historical contingency in community assembly: integrating niches, species pools, and priority effects. Annu. Rev. Ecol. Evol. Syst. 46, 1–23 (2015).

    Article  Google Scholar 

  117. 117.

    Gleason, H. A. Further views on the succession-concept. Ecology 8, 299–326 (1927).

    Article  Google Scholar 

  118. 118.

    Debray, R. et al. Priority effects in microbiome assembly. Nat. Rev. Microbiol. https://doi.org/10.1038/s41579-021-00604-w (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  119. 119.

    Sprockett, D., Fukami, T. & Relman, D. A. Role of priority effects in the early-life assembly of the gut microbiota. Nat. Rev. Gastroenterol. Hepatol. 15, 197–205 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  120. 120.

    Martínez, I. et al. Experimental evaluation of the importance of colonization history in early-life gut microbiota assembly. eLife 7, e36521 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  121. 121.

    Johnson, A. J. et al. Daily sampling reveals personalized diet-microbiome associations in humans. Cell Host Microbe 25, 789–802.e5 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  122. 122.

    Smits, S. A. et al. Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania. Science 357, 802–806 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  123. 123.

    Knutie, S. A., Wilkinson, C. L., Kohl, K. D. & Rohr, J. R. Early-life disruption of amphibian microbiota decreases later-life resistance to parasites. Nat. Commun. 8, 86 (2017).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  124. 124.

    Arnold, I. C. et al. Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells. J. Clin. Invest. 121, 3088–3093 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  125. 125.

    Lynch, J. B. & Hsiao, E. Y. Microbiomes as sources of emergent host phenotypes. Science 365, 1405–1409 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  126. 126.

    Mayoral-Peña, Z., Álvarez-Martínez, R., Fornoni, J. & Garrido, E. In Evolutionary Ecology of Plant-Herbivore Interaction (eds Núñez-Farfán, J. & Valverde, P. L.) 135–146 (Springer International Publishing, 2020).

  127. 127.

    Lindsay, E. C., Metcalfe, N. B. & Llewellyn, M. S. The potential role of the gut microbiota in shaping host energetics and metabolic rate. J. Anim. Ecol. 89, 2415–2426 (2020).

    PubMed  Article  Google Scholar 

  128. 128.

    Vaelli, P. M. et al. The skin microbiome facilitates adaptive tetrodotoxin production in poisonous newts. eLife 9, e53898 (2020). This work demonstrates that the toxic newt phenotype is shaped through the combination of toxin-producing skin microorganisms and toxin-tolerant host genotypes.

    PubMed  PubMed Central  Article  Google Scholar 

  129. 129.

    Thaiss, C. A. et al. Microbiota diurnal rhythmicity programs host transcriptome oscillations. Cell 167, 1495–1510.e12 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  130. 130.

    Nichols, R. G. & Davenport, E. R. The relationship between the gut microbiome and host gene expression: a review. Hum. Genet. 140, 747–760 (2021).

    CAS  PubMed  Article  Google Scholar 

  131. 131.

    Chen, H. et al. A forward chemical genetic screen reveals gut microbiota metabolites that modulate host physiology. Cell 177, 1217–1231.e18 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  132. 132.

    Yano, J. M. et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161, 264–276 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  133. 133.

    Meisel, J. S. et al. Commensal microbiota modulate gene expression in the skin. Microbiome 6, 20 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  134. 134.

    Rooks, M. G. & Garrett, W. S. Gut microbiota, metabolites and host immunity. Nat. Rev. Immunol. 16, 341–352 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  135. 135.

    Sanchez, H. N. et al. B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids. Nat. Commun. 11, 60 (2020). This study shows that microbiota-produced SCFAs impair intestinal and systemic antibody responses upregulating micro RNAs that target immune genes through inhibition of histone deacetylation.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  136. 136.

    Bonder, M. J. et al. The effect of host genetics on the gut microbiome. Nat. Genet. 48, 1407–1412 (2016).

    CAS  PubMed  Article  Google Scholar 

  137. 137.

    Poole, A. C. et al. Human Salivary amylase gene copy number impacts oral and gut microbiomes. Cell Host Microbe 25, 553–564.e7 (2019).

    CAS  PubMed  Article  Google Scholar 

  138. 138.

    Rothschild, D. et al. Environment dominates over host genetics in shaping human gut microbiota. Nature 555, 210–215 (2018).

    CAS  PubMed  Article  Google Scholar 

  139. 139.

    Carmody, R. N. et al. Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe 17, 72–84 (2015).

    CAS  PubMed  Article  Google Scholar 

  140. 140.

    Wagner, M. R. et al. Host genotype and age shape the leaf and root microbiomes of a wild perennial plant. Nat. Commun. 7, 12151 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  141. 141.

    Qanbari, S. et al. Genetics of adaptation in modern chicken. PLoS Genet. 15, e1007989 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  142. 142.

    Weissbrod, O., Rothschild, D., Barkan, E. & Segal, E. Host genetics and microbiome associations through the lens of genome wide association studies. Curr. Opin. Microbiol. 44, 9–19 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  143. 143.

    Suzuki, T. A. Links between natural variation in the microbiome and host fitness in wild mammals. Integr. Comp. Biol. 57, 756–769 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  144. 144.

    Gould, A. L. et al. Microbiome interactions shape host fitness. Proc. Natl Acad. Sci. U. S. A. 115, E11951–E11960 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  145. 145.

    Rosshart, S. P. et al. Wild mouse gut microbiota promotes host fitness and improves disease resistance. Cell 171, 1015–1021.e13 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  146. 146.

    Cooper, R. O., Vavra, J. M. & Cressler, C. E. Targeted manipulation of abundant and rare taxa in the daphnia magna microbiota with antibiotics impacts host fitness differentially. mSystems 6, e00916-20 (2021).

    PubMed  Article  PubMed Central  Google Scholar 

  147. 147.

    Moeller, A. H. & Sanders, J. G. Roles of the gut microbiota in the adaptive evolution of mammalian species. Philos. Trans. R. Soc. Lond. B Biol. Sci. 375, 20190597 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  148. 148.

    Fontaine, S. S. & Kohl, K. D. Optimal integration between host physiology and functions of the gut microbiome. Philos. Trans. R. Soc. Lond. B Biol. Sci. 375, 20190594 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  149. 149.

    Suzuki, T. A. & Ley, R. E. The role of the microbiota in human genetic adaptation. Science 370, aaz6827 (2020).

    Article  CAS  Google Scholar 

  150. 150.

    Alberdi, A., Aizpurua, O., Bohmann, K., Zepeda-Mendoza, M. L. & Gilbert, M. T. P. Do vertebrate gut metagenomes confer rapid ecological adaptation? Trends Ecol. Evol. 31, 689–699 (2016).

    PubMed  Article  Google Scholar 

  151. 151.

    Wang, G.-H. et al. Changes in microbiome confer multigenerational host resistance after sub-toxic pesticide exposure. Cell Host Microbe 27, 213–224.e7 (2020). This paper shows that the gut microbiota confers Nasonia wasps with resistance towards pesticides and that this acquired trait shapes their genomic evolutionary features across multiple generations.

    CAS  PubMed  Article  Google Scholar 

  152. 152.

    van Opstal, E. J. & Bordenstein, S. R. Rethinking heritability of the microbiome. Science 349, 1172–1173 (2015).

    PubMed  Article  Google Scholar 

  153. 153.

    Douglas, G. M., Bielawski, J. P. & Langille, M. G. I. Re-evaluating the relationship between missing heritability and the microbiome. Microbiome 8, 87 (2020).

    PubMed  PubMed Central  Article  Google Scholar 

  154. 154.

    Khan, A. A. et al. Polymorphic immune mechanisms regulate commensal repertoire. Cell Rep. 29, 541–550.e4 (2019). This study shows that genetic variants of innate and adaptive immunity genes shape distinct microbial communities through the production of distinct immunoglobulins some microorganisms use for colonizing the mucosal barrier.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  155. 155.

    Davenport, E. R. Genetic variation shapes murine gut microbiota via immunity. Trends Immunol. 41, 1–3 (2020).

    CAS  PubMed  Article  Google Scholar 

  156. 156.

    Van Vliet, S. & Doebeli, M. The role of multilevel selection in host microbiome evolution. Proc. Natl Acad. Sci. USA 116, 20591–20597 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  157. 157.

    Groussin, M., Mazel, F. & Alm, E. J. Co-evolution and co-speciation of host-gut bacteria systems. Cell Host Microbe 28, 12–22 (2020).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  158. 158.

    Meissner, A. et al. Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis. Nucleic Acids Res. 33, 5868–5877 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  159. 159.

    Beaulaurier, J. et al. Metagenomic binning and association of plasmids with bacterial host genomes using DNA methylation. Nat. Biotechnol. 36, 61–69 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  160. 160.

    Ma, F., Jiang, S. & Zhang, C.-Y. Recent advances in histone modification and histone modifying enzyme assays. Expert Rev. Mol. Diagn. 19, 27–36 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  161. 161.

    DeMaere, M. Z. & Darling, A. E. bin3C: exploiting Hi-C sequencing data to accurately resolve metagenome-assembled genomes. Genome Biol. 20, 46 (2019).

    PubMed  PubMed Central  Article  Google Scholar 

  162. 162.

    Kent, A. G., Vill, A. C., Shi, Q., Satlin, M. J. & Brito, I. L. Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C. Nat. Commun. 11, 4379 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  163. 163.

    Hammer, T. J., Janzen, D. H., Hallwachs, W., Jaffe, S. P. & Fierer, N. Caterpillars lack a resident gut microbiome. Proc. Natl Acad. Sci. USA 114, 9641–9646 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  164. 164.

    Oliver, K. M., Moran, N. A. & Hunter, M. S. Costs and benefits of a superinfection of facultative symbionts in aphids. Proc. Biol. Sci. 273, 1273–1280 (2006).

    PubMed  PubMed Central  Google Scholar 

  165. 165.

    Song, S. J. et al. Comparative analyses of vertebrate gut microbiomes reveal convergence between birds and bats. MBio 11, e02901-19 (2020).

    PubMed  PubMed Central  Article  Google Scholar 

  166. 166.

    Krediet, C. J., Ritchie, K. B., Paul, V. J. & Teplitski, M. Coral-associated micro-organisms and their roles in promoting coral health and thwarting diseases. Proc. Biol. Sci. 280, 20122328 (2013).

    PubMed  PubMed Central  Google Scholar 

  167. 167.

    Brune, A. Symbiotic digestion of lignocellulose in termite guts. Nat. Rev. Microbiol. 12, 168–180 (2014).

    CAS  PubMed  Article  Google Scholar 

  168. 168.

    McCann, J. C., Wickersham, T. A. & Loor, J. J. High-throughput methods redefine the rumen microbiome and its relationship with nutrition and metabolism. Bioinform. Biol. Insights 8, 109–125 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  169. 169.

    Rosshart, S. P. et al. Laboratory mice born to wild mice have natural microbiota and model human immune responses. Science 365, aaw4361 (2019).

    Article  CAS  Google Scholar 

  170. 170.

    Niehus, R., Mitri, S., Fletcher, A. G. & Foster, K. R. Migration and horizontal gene transfer divide microbial genomes into multiple niches. Nat. Commun. 6, 8924 (2015).

    CAS  PubMed  Article  Google Scholar 

  171. 171.

    Carrier, T. J. & Reitzel, A. M. The hologenome across environments and the implications of a host-associated microbial repertoire. Front. Microbiol. 8, 802 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  172. 172.

    Mushegian, A. A. & Ebert, D. Rethinking ‘mutualism’ in diverse host-symbiont communities. Bioessays 38, 100–108 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  173. 173.

    Pereira, F. C. & Berry, D. Microbial nutrient niches in the gut. Environ. Microbiol. 19, 1366–1378 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  174. 174.

    Erin Chen, Y., Fischbach, M. A. & Belkaid, Y. Skin microbiota–host interactions. Nature 553, 427–436 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  175. 175.

    Earley, A. M., Graves, C. L. & Shiau, C. E. Critical role for a subset of intestinal macrophages in shaping gut microbiota in adult Zebrafish. Cell Rep. 25, 424–436 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  176. 176.

    Kartzinel, T. R., Hsing, J. C. & Musili, P. M. Covariation of diet and gut microbiome in African megafauna. Proc. Natl Acad. Sci. USA 116, 23588–23593 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  177. 177.

    Perofsky, A. C., Lewis, R. J., Abondano, L. A., Di Fiore, A. & Meyers, L. A. Hierarchical social networks shape gut microbial composition in wild Verreaux’s sifaka. Proc. Biol. Sci. 284, 20172274 (2017).

    PubMed  PubMed Central  Google Scholar 

  178. 178.

    Asnicar, F. et al. Studying vertical microbiome transmission from mothers to infants by strain-level metagenomic profiling. mSystems 2, e00164-16 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  179. 179.

    Storelli, G. et al. Lactobacillus plantarum promotes Drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing. Cell Metab. 14, 403–414 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  180. 180.

    Johnson, K. V.-A. & Foster, K. R. Why does the microbiome affect behaviour? Nat. Rev. Microbiol. 16, 647–655 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  181. 181.

    Davidson, G. L., Raulo, A. & Knowles, S. C. L. Identifying microbiome-mediated behaviour in wild vertebrates. Trends Ecol. Evol. 35, 972–980 (2020).

    PubMed  Article  PubMed Central  Google Scholar 

  182. 182.

    Zhang, Y.-J. et al. Impacts of gut bacteria on human health and diseases. Int. J. Mol. Sci. 16, 7493–7519 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  183. 183.

    Flint, H. J., Scott, K. P., Duncan, S. H., Louis, P. & Forano, E. Microbial degradation of complex carbohydrates in the gut. Gut Microbes 3, 289–306 (2012).

    PubMed  PubMed Central  Article  Google Scholar 

  184. 184.

    Nicholson, J. K. et al. Host-gut microbiota metabolic interactions. Science 336, 1262–1267 (2012).

    CAS  Article  Google Scholar 

  185. 185.

    Fellows, R. et al. Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. Nat. Commun. 9, 105 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  186. 186.

    Neuman, H., Debelius, J. W., Knight, R. & Koren, O. Microbial endocrinology: the interplay between the microbiota and the endocrine system. FEMS Microbiol. Rev. 39, 509–521 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank the Danish National Research Foundation award DNRF143 ‘A Center for Evolutionary Hologenomics’ for funding their research. A.A. acknowledges Lundbeckfonden grant R250-2017-1351. A.A., M.T.L. and M.T.P.G. were supported by the European Union (H2020-SFS-2018-1 project HoloFood-817729). M.T.L. and M.T.P.G. acknowledge the FHF (Norwegian Seafood Research Fund; “HoloFish”, grant No. 901436). S.B.A. acknowledges Lundbeckfonden Fellowship R335-2019-1513 ‘Understanding the Health Effects of Microbial Interactions’ and Independent Research Council Denmark Sapere Aude grant 9064-00029B ‘Understanding the Effects of Microbial Interactions on Host Health’.

Author information

Affiliations

Authors

Contributions

A.A. researched data for the article. All authors made substantial contributions to discussions of the content and writing the article and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Antton Alberdi.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Genetics thanks S. Borderstein, T. Bosch and M. van Oppen for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Metagenotype

The specific state of the microbial metagenome characterized at a particular moment and at a given resolution.

Hologenotype

The entire genetic constitution of an individual eukaryotic organism and its associated microorganisms characterized at a given moment and at a given resolution.

Metagenome-assembled genomes

(MAGs). Partial or semi-complete draft bacterial genomes reconstructed through metagenomic assembly and binning from samples containing mixtures of microbial taxa.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Alberdi, A., Andersen, S.B., Limborg, M.T. et al. Disentangling host–microbiota complexity through hologenomics. Nat Rev Genet (2021). https://doi.org/10.1038/s41576-021-00421-0

Download citation

Search

Quick links