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The microbiome beyond the horizon of ecological and evolutionary theory


The ecological and evolutionary study of community formation, diversity, and stability is rooted in general theory and reinforced by decades of system-specific empirical work. Deploying these ideas to study the assembly, complexity, and dynamics of microbial communities living in and on eukaryotes has proved seductive, but challenging. The success of this research endeavour depends on our capacity to observe and characterize the distributions, abundances, and functional traits of microbiota, representing an array of technical and analytical challenges. Furthermore, a number of unique characteristics of microbial species, such as horizontal gene transfer, the production of public goods, toxin and antibiotic production, rapid evolution, and feedbacks between the microbiome and its host, are not easily accommodated by current ecological and evolutionary theory. Here we highlight potential pitfalls in the application of existing theoretical tools without careful consideration of the unique complexities of the microbiome, focusing particularly on the issue of human health, and anchoring our discussion in existing empirical evidence.

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  1. 1.

    Magalhães, A. P., Azevedo, N. F., Pereira, M. O. & Lopes, S. P. The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy. Appl. Microbiol. Biotech. 100, 1163–1181 (2016).

  2. 2.

    Vatanen, T. et al. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell 165, 842–853 (2016).

  3. 3.

    Blanton, L. V. et al. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science 351, aad3311 (2016).

  4. 4.

    Vandenkoornhuyse, P., Quaiser, A., Duhamel, M., Le Van, A. & Dufresne, A. The importance of the microbiome of the plant holobiont. New Phytol. 206,1196–1206 (2015).

  5. 5.

    Yarza, P. et al. Uniting the classification of cultured and uncultured bacteria and archaea using 16S rRNA gene sequences. Nat. Rev. Microbiol. 12, 635–645 (2014).

  6. 6.

    Jones, M. B. et al. Library preparation methodology can influence genomic and functional predictions in human microbiome research. Proc. Natl Acad. Sci. USA 112, 14024–14029 (2015).

  7. 7.

    Costello, E. K., Stagaman, K., Dethlefsen, L., Bohannan, B. J. & Relman, D. A. The application of ecological theory toward an understanding of the human microbiome. Science 336, 1255–1262 (2012).

  8. 8.

    Coyte, K. Z., Schluter, J. & Foster, K. R. The ecology of the microbiome: networks, competition, and stability. Science 350, 663–666 (2015).

  9. 9.

    Beaume, M. et al. Rapid adaptation drives invasion of airway donor microbiota by Pseudomonas after lung transplantation. Sci. Rep. 7, 40309 (2017).

  10. 10.

    Koenig, J. E. et al. Succession of microbial consortia in the developing infant gut microbiome. Proc. Natl Acad. Sci. USA 108, 4578–4585 (2011).

  11. 11.

    Matamoros, S., Gras-Leguen, C., Le Vacon, F. & Potel, G. & de La Cochetiere, M.-F. Development of intestinal microbiota in infants and its impact on health. Trends MicroBiol. 21, 167–173 (2013).

  12. 12.

    Vallès, Y. et al. Microbial succession in the gut: directional trends of taxonomic and functional change in a birth cohort of Spanish infants. PLoS Genet. 10, e1004406 (2014).

  13. 13.

    Langdon, A., Crook, N. & Dantas, G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Gen. Med. 8, 39 (2016).

  14. 14.

    Stahringer, S. S. et al. Nurture trumps nature in a longitudinal survey of salivary bacterial communities in twins from early adolescence to early adulthood. Gen. Res. 22, 2146–2152 (2012).

  15. 15.

    David, L. A. et al. Gut microbial succession follows acute secretory diarrhea in humans. mBio 6, e00381–e00315 (2015).

  16. 16.

    Seedorf, H. et al. Bacteria from diverse habitats colonize and compete in the mouse gut. Cell 159, 253–266 (2014).

  17. 17.

    Whiteson, K. L. et al. The upper respiratory tract as a microbial source for pulmonary infections in cystic fibrosis. Parallels from island biogeography. Am. J. Respir. Crit. Care Med. 189, 1309–1315 (2014).

  18. 18.

    Chesson, P. Mechanisms of maintenance of species diversity. Ann. Rev. Ecol. Syst. 31, 343–366 (2000).

  19. 19.

    Hutchinson, G. E. Homage to Santa Rosalia or why are there so many kinds of animals? Am. Nat. 93, 145–159 (1959).

  20. 20.

    Maldonado-Gómez, M. X. et al. Stable engraftment of Bifidobacterium longum AH1206 in the human gut depends on individualized features of the resident microbiome. Cell Host Microb. 20, 515–526 (2016).

  21. 21.

    Plichta, D. R. et al. Transcriptional interactions suggest niche segregation among microorganisms in the human gut. Nat. Microbiol. 1, 16152 (2016).

  22. 22.

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

  23. 23.

    Levy, R. & Borenstein, E. Metabolic modeling of species interaction in the human microbiome elucidates community-level assembly rules. Proc. Natl Acad. Sci. USA 110, 12804–12809 (2013).

  24. 24.

    Faust, K. & Raes, J. Microbial interactions: from networks to models. Nat. Rev. Microbiol. 10, 538–550 (2012).

  25. 25.

    Kamneva, O. K. Genome composition and phylogeny of microbes predict their co-occurrence in the environment. PLoS Comput. Biol. 13, e1005366 (2017).

  26. 26.

    Welch, J. L. M., Rossetti, B. J., Rieken, C. W., Dewhirst, F. E. & Borisy, G. G. Biogeography of a human oral microbiome at the micron scale. Proc. Natl Acad. Sci. USA 113, E791–E800 (2016).

  27. 27.

    Burns, A. R. et al. Contribution of neutral processes to the assembly of gut microbial communities in the zebrafish over host development. ISME J. 10, 655–664 (2015).

  28. 28.

    Venkataraman, A. et al. Application of a neutral community model to assess structuring of the human lung microbiome. mBio 6, e02284–e02214 (2015).

  29. 29.

    O’Dwyer, J. P., Kembel, S. W. & Sharpton, T. J. Backbones of evolutionary history test biodiversity theory for microbes. Proc. Natl Acad. Sci. USA 112, 8356–8361 (2015).

  30. 30.

    Li, L. & Ma, Z. S. Testing the neutral theory of biodiversity with human microbiome datasets. Sci. Rep. 6, 31448 (2016).

  31. 31.

    Stein, R. R. et al. Ecological modeling from time-series inference: insight into dynamics and stability of intestinal microbiota. PLoS Comput. Biol. 9, e1003388 (2013).

  32. 32.

    Jeraldo, P. et al. Quantification of the relative roles of niche and neutral processes in structuring gastrointestinal microbiomes. Proc. Natl Acad. Sci. USA 109, 9692–9698 (2012).

  33. 33.

    Welsh, R. M. et al. Bacterial predation in a marine host-associated microbiome. ISME J. 10, 1540–1544 (2015).

  34. 34.

    Barr, J. J. et al. Bacteriophage adhering to mucus provide a non-host-derived immunity. Proc. Natl Acad. Sci. USA 110,10771–10776 (2013).

  35. 35.

    Koskella, B. Phage-mediated selection on microbiota of a long-lived host. Curr. Biol. 23, 1256–1260 (2013).

  36. 36.

    Reyes, A., Wu, M., McNulty, N. P., Rohwer, F. L. & Gordon, J. I. Gnotobiotic mouse model of phage–bacterial host dynamics in the human gut. Proc. Natl Acad. Sci. USA 110, 20236–20241 (2013).

  37. 37.

    Seed, K. D. et al. Evolutionary consequences of intra-patient phage predation on microbial populations. eLife 3, e03497 (2014).

  38. 38.

    Meaden, S., Paszkiewicz, K. & Koskella, B. The cost of phage resistance in a plant pathogenic bacterium is context‐dependent. Evolution 69, 1321–1328 (2015).

  39. 39.

    Lin, T.-Y. et al. A T3 and T7 recombinant phage acquires efficient adsorption and a broader host range. PLoS ONE 7, e30954 (2012).

  40. 40.

    Pride, D. T. et al. Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome. ISME J. 6, 915–926 (2012).

  41. 41.

    Hastings, A. et al. Ecosystem engineering in space and time. Ecol. Lett. 10, 153–164 (2007).

  42. 42.

    Smith, A. H. et al. Patterns, causes and consequences of defensive microbiome dynamics across multiple scales. Mol. Ecol. 24, 1135–1149 (2015).

  43. 43.

    Widder, S. et al. Challenges in microbial ecology: building predictive understanding of community function and dynamics. ISME J. 10, 2557–2568 (2016).

  44. 44.

    Agler, M. et al. Microbial hub taxa link host and abiotic factors to plant microbiome variation. PLoS Biol. 14, e1002352 (2016).

  45. 45.

    Greenblum, S., Turnbaugh, P. J. & Borenstein, E. Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease. Proc. Natl Acad. Sci. USA 109,594–599 (2012).

  46. 46.

    Burke, C., Steinberg, P., Rusch, D., Kjelleberg, S. & Thomas, T. Bacterial community assembly based on functional genes rather than species. Proc. Natl Acad. Sci. USA 108, 14288–14293 (2011).

  47. 47.

    Liu, L. et al. The human microbiome: a hot spot of microbial horizontal gene transfer. Genomics 100, 265–270 (2012).

  48. 48.

    Smillie, C. S. et al. Ecology drives a global network of gene exchange connecting the human microbiome. Nature 480, 241–244 (2011).

  49. 49.

    Schluter, J., Nadell, C. D., Bassler, B. L. & Foster, K. R. Adhesion as a weapon in microbial competition. ISME J. 9, 139–149 (2015).

  50. 50.

    Anacker, B. L. & Strauss, S. Y. Ecological similarity is related to phylogenetic distance between species in a cross‐niche field transplant experiment. Ecology 97, 1807–1818 (2016).

  51. 51.

    Lozupone, C. & Knight, R. UniFrac: a new phylogenetic method for comparing microbial communities. Appl. Environ. Microbiol. 71, 8228–8235 (2005).

  52. 52.

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

  53. 53.

    Ellers, J., Toby Kiers, E., Currie, C. R., McDonald, B. R. & Visser, B. Ecological interactions drive evolutionary loss of traits. Ecol. Lett. 15, 1071–1082 (2012).

  54. 54.

    Morris, J. J., Lenski, R. E. & Zinser, E. R. The Black Queen hypothesis: evolution of dependencies through adaptive gene loss. mBio 3, e00036–12 (2012).

  55. 55.

    Rashid, M.-U. et al. Determining the long-term effect of antibiotic administration on the human normal intestinal microbiota using culture and pyrosequencing methods. Clin. Infect. Dis. 60, S77–S84 (2015).

  56. 56.

    MacIntyre, D. A. et al. The vaginal microbiome during pregnancy and the postpartum period in a European population. Sci. Rep. 5, 8988 (2015).

  57. 57.

    Vieira-Silva, S. et al. Species–function relationships shape ecological properties of the human gut microbiome. Nat. Microbiol. 1, 16088 (2016).

  58. 58.

    Ross‐Gillespie, A., Gardner, A., West, S. A. & Griffin, A. S. Frequency dependence and cooperation: theory and a test with bacteria. Am. Nat. 170, 331–342 (2007).

  59. 59.

    Darch, S. E., West, S. A., Winzer, K. & Diggle, S. P. Density-dependent fitness benefits in quorum-sensing bacterial populations. Proc. Natl Acad. Sci. USA 109, 8259–8263 (2012).

  60. 60.

    Holt, R. D., Lawton, J. H., Polis, G. A. & Martinez, N. D. Trophic rank and the species–area relationship. Ecology 80, 1495–1504 (1999).

  61. 61.

    Zilber-Rosenberg, I. & Rosenberg, E. Role of microorganisms in the evolution of animals and plants: the hologenome theory of evolution. FEMS Microbiol. Rev. 32, 723–735 (2008).

  62. 62.

    Goodrich, J. K. et al. Genetic determinants of the gut microbiome in UK twins. Cell Host Microb. 19, 731–743 (2016).

  63. 63.

    Turpin, W. et al. Association of host genome with intestinal microbial composition in a large healthy cohort. Nat. Genet. 48, 1413–1417 (2016).

  64. 64.

    Milani, C. et al. Exploring vertical transmission of bifidobacteria from mother to child. Appl. Environ. Microbiol. 81, 7078–7087 (2015).

  65. 65.

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

  66. 66.

    Ewald, P. W. Transmission modes and evolution of the parasitism–mutualism continuum. Ann. NY Acad. Sci. 503, 295–306 (1987).

  67. 67.

    Browne, H. P. et al. Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature 533, 543–546 (2016).

  68. 68.

    Blaser, M. J. & Falkow, S. What are the consequences of the disappearing human microbiota? Nat. Rev. Microbiol. 7, 887–894 (2009).

  69. 69.

    Leibold, M. A. et al. The metacommunity concept: a framework for multi‐scale community ecology. Ecol. Lett. 7, 601–613 (2004).

  70. 70.

    Aagaard, K. et al. The placenta harbors a unique microbiome. Sci. Transl. Med. 6, 237ra265 (2014).

  71. 71.

    Perez-Muñoz, M. E., Arrieta, M.-C., Ramer-Tait, A. E. & Walter, J. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome 5, 48 (2017).

  72. 72.

    Jiménez, E. et al. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Curr. Microbiol. 51, 270–274 (2005).

  73. 73.

    Dominguez-Bello, M. G. et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl Acad. Sci USA 107, 11971–11975 (2010).

  74. 74.

    Albesharat, R., Ehrmann, M. A., Korakli, M., Yazaji, S. & Vogel, R. F. Phenotypic and genotypic analyses of lactic acid bacteria in local fermented food, breast milk and faeces of mothers and their babies. Syst. Appl. Microbiol. 34, 148–155 (2011).

  75. 75.

    Moeller, A. H. et al. Cospeciation of gut microbiota with hominids. Science 353,380–382 (2016).

  76. 76.

    Song, S. J. et al. Cohabiting family members share microbiota with one another and with their dogs. eLife 2, e00458 (2013).

  77. 77.

    Meadow, J. F., Bateman, A. C., Herkert, K. M., O’Connor, T. K. & Green, J. L. Significant changes in the skin microbiome mediated by the sport of roller derby. PeerJ 1, e53 (2013).

  78. 78.

    Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352, 560–564 (2016).

  79. 79.

    Clemente, J. C. et al. The microbiome of uncontacted Amerindians. Sci. Adv. 1, e1500183 (2015).

  80. 80.

    Moeller, A. H. et al. Rapid changes in the gut microbiome during human evolution. Proc. Natl Acad. Sci. USA 111, 16431–16435 (2014).

  81. 81.

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

  82. 82.

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

  83. 83.

    Rillig, M. C. et al. Interchange of entire communities: microbial community coalescence. Trends Ecol. Evol. 30, 470–476 (2015).

  84. 84.

    Dunne, J. A., Williams, R. J. & Martinez, N. D. Network structure and biodiversity loss in food webs: robustness increases with connectance. Ecol. Lett. 5, 558–567 (2002).

  85. 85.

    Fisher, C. K. & Mehta, P. Identifying keystone species in the human gut microbiome from metagenomic timeseries using sparse linear regression. PLoS ONE 9, e102451 (2014).

  86. 86.

    Davenport, E. R. et al. Genome-wide association studies of the human gut microbiota. PLoS ONE 10, e0140301 (2015).

  87. 87.

    Frenkel, E. S. & Ribbeck, K. Salivary mucins promote the coexistence of competing oral bacterial species. ISME J. 11, 1286–1290 (2017).

  88. 88.

    Desai, M. S. et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167, 1339–1353.e21 (2016).

  89. 89.

    Vaishnava, S. et al. The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science 334, 255–258 (2011).

  90. 90.

    Zivkovic, A. M., German, J. B., Lebrilla, C. B. & Mills, D. A. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc. Natl Acad. Sci. USA 108, 4653–4658 (2011).

  91. 91.

    Cullen, T. et al. Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation. Science 347, 170–175 (2015).

  92. 92.

    Gensollen, T., Iyer, S. S., Kasper, D. L. & Blumberg, R. S. How colonization by microbiota in early life shapes the immune system. Science 352, 539–544 (2016).

  93. 93.

    Liu, S. et al. The host shapes the gut microbiota via fecal microRNA. Cell Host Microb. 19, 32–43 (2016).

  94. 94.

    Modi, S. R., Lee, H. H., Spina, C. S. & Collins, J. J. Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome. Nature 499, 219–222 (2013).

  95. 95.

    Muñoz-Tamayo, R. et al. Kinetic modelling of lactate utilization and butyrate production by key human colonic bacterial species. FEMS Microbiol. Ecol. 76, 615–624 (2011).

  96. 96.

    Lahti, L., Salojärvi, J., Salonen, A., Scheffer, M. & de Vos, W. M. Tipping elements in the human intestinal ecosystem. Nat. Commun. 5, 4344 (2014).

  97. 97.

    Byrd, A. L. & Segre, J. A. Adapting Koch's postulates. Science 351, 224–226 (2016).

  98. 98.

    Eren, A. M. et al. A single genus in the gut microbiome reflects host preference and specificity. ISME J. 9, 90–100 (2015).

  99. 99.

    Scanlan, P. D., Knight, R., Song, S. J., Ackermann, G. & Cotter, P. D. Prevalence and genetic diversity of Blastocystis in family units living in the United States. Infect. Genet. Evol. 45, 95–97 (2016).

  100. 100.

    Baker, J. L., Bor, B., Agnello, M., Shi, W. & He, X. Ecology of the oral microbiome: beyond bacteria. Trends Microbiol. 25, 362–374 (2017).

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We thank the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security and the Fogarty International Center, National Institutes of Health and Wellcome Trust for funding the workshop from which this manuscript emerged, and all workshop participants (M. Blaser; S. Brown; A. Buckling; S. Chen; D. Churamani; M. Claesson; W. Cookson; M. Cox; K. Coyte; J. Curtis; K. Davies; R. De Weirdt; J. Dore; S. D. Ehrlich; M. Ferguson; H. Flint; K. Foster; B. Grenfell; N. Ilott; A. Johnson; A. Kuspa; R. La Ragione; T. Lawley; S. Levin; J. M. Welch; K. Moses; J. Parkhill; P Rainey; J. Segre; D. Spratt; C. Steves; Z. Takats; C. Tropini; M. Tunney; A. Wallace; A. Watson; D. Weinkove; C. Weller; P. Wilmes; N. Wingreen; J. Xavier); as well as organizers, D. Cannon and A. Cave,for further discussion of the manuscript.

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B.K., L.J.H. and C.J.E.M. all contributed to the formation of ideas and writing of this manuscript.

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The authors declare no competing financial interests.

Correspondence to Britt Koskella.

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Fig. 1: Illustration of the various -omics approaches and the advantages of combining methods to understand microbiome function.
Fig. 2: Evolutionary and ecological principles influencing microbiome establishment, stability, and transmission among generations.